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Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the “Lifespan and Life Course Research: integrating strategies” “Un-Meeting” to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.
OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.
Electronic platforms provide an opportunity to improve the informed consent (IC) process by permitting elements shown to increase research participant understanding and satisfaction, such as graphics, self-pacing, meaningful engagement, and access to additional information on demand. However, including these elements can pose operational and regulatory challenges for study teams and institutional review boards (IRBs) responsible for the ethical conduct and oversight of research. We examined the experience of two study teams at Alzheimer’s Disease Research Centers who chose to move from a paper-based IC process to an electronic informed consent (eIC) process to highlight some of these complexities and explore how IRBs and study teams can navigate them. Here, we identify the key regulations that should be considered when developing and using an eIC process as well as some of the operational considerations eIC presents related to IRB review and how they can be addressed.
Research characterising the gut microbiota in different populations and diseases has mushroomed since the advent of next-generation sequencing techniques. However, there has been less emphasis on the impact of dietary fibres and other dietary components that influence gut microbial metabolic activities. Dietary fibres are the main energy source for gut bacteria. However, fibres differ in their physicochemical properties, their effects on the gut and their fermentation characteristics. The diversity of carbohydrates and associated molecules in fibre-rich foods can have a major influence on microbiota composition and production of bioactive molecules, for example SCFAs and phenolic acids. Several of these microbial metabolites may influence the functions of body systems including the gut, liver, adipose tissues and brain. Dietary fibre intake recommendations have recently been increased (to 30 g daily) in response to growing obesity and other health concerns. Increasing intakes of specific fibre and plant food sources may differentially influence the bacteria and their metabolism. However, in vitro studies show great individual variability in the response of the gut microbiota to different fibres and fibre combinations, making it difficult to predict which foods or food components will have the greatest impact on levels of bioactive molecules produced in the colon of individuals. Greater understanding of individual responses to manipulation of the diet, in relation to microbiome composition and production of metabolites with proven beneficial impact on body systems, would allow the personalised approach needed to best promote good health.
Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
Despite increasing attention to the importance of diverse research participants, success across the translational research spectrum remains limited. To assess investigator and research team training needs, we conducted a web-based survey exploring barriers in knowledge and practice. Respondents (n = 279) included those affiliated with the University of Wisconsin Institute for Clinical and Translational Research (ICTR). Although all respondents reported an abstract belief in the importance of diversity, factors associated with higher levels of best practices knowledge and implementation included: (1) use of federal funding; (2) having fewer years of experience; (3) recruiting healthy participants; and (4) having recruitment training.
Interactions between polyphenols and non-digestible carbohydrates (NDC) can impact on polyphenolic metabolites bioavailability, including phenolic acids. The BLEND2 trial (NCT03840746) aims to study longer-term interactions of a flavonoid-rich food with/without NDC on microbiota metabolites and cardiometabolic markers. Trial feasibility using a bespoke food was tested.
Material and Methods
The soup was developed locally containing cherry tomatoes, tomato puree, red onion, fresh lovage, with/without the NDC inulin (10g), but improved and processed with Campden BRI, Chipping Campden, UK. The final product (~400g/ tin) was evaluated with VAS scales (0–10) for appearance, smell, taste and overall palatability, and flavonoid content evaluated using liquid chromatography-mass spectrometry. The 3-arm parallel randomised blinded design (control soup, soup + inulin, habitual diet control) recruited self-reported healthy participants (BMI > 25, 40–70y) with urine, blood, faecal samples collected at baseline, 3-week, 6-weeks.
Both soups scored similarly (n = 8 testers) for visual appeal (with inulin 5.1 ± 2.1; without 4.5 ± 2.0); smell (with 5.9 ± 1.7; without 5.4 ± 0.8); taste (with 6.6 ± 2.0; without 5.5 ± 2.3), aftertaste (with 6.3 ± 2.9; without 5.4 ± 2.3) and overall palatability (with 7.0 ± 1.9; without 6.1 ± 2.1).
The soups (A&B), 1 tin/day, provide 68.5 ± 10.9 mg total flavonoids (soup A n = 3, quercetin equivalents) and 74.0 ± 16.1 mg (soup B, n = 3): quercetin (A 1.2 ± 0.1 mg; B 1.3 ± 0.6 mg), quercetin-4-glucoside (A 3.9 ± 1.0 mg; B 4.1 ± 1.9 mg), quercetin-3-rutinoside (A 23.0 ± 3.2 mg; B 20.5 ± 1.0 mg), quercetin 3,4-diglucosides (A 40.5 ± 6.9 mg; B 48.2 ± 14.9 mg).
Following notes of interest (n = 415), n = 111 attended screening, n = 34 did not proceed (medications, opt-out; 31%). Participants (n = 77) are mostly British (79%), median age 56y (IQR 49-62) with a median BMI of 31 (IQR 28-35). Dropout was low (12%) and early in the study (personal issues, n = 2; gastrointestinal issues, n = 2; failure to comply with protocol, n = 2; acid reflux symptoms, n = 1; dislike of test food, n = 1). Adverse events included acid reflux/heartburn (n = 4), gastrointestinal distress (n = 3) accounting for 3 drop-outs.
To date, urine, blood and faecal samples (study day or day + 1) were collected at all timepoints, for all participants. Participation (soup arms) has not led to body weight or blood lipids changes compared to control group.
The protocol for this 6-week trial has proved feasible with lower dropout than expected. Soup flavonoid content representing ~16% of average European flavonoid intakes, with inulin (10g) half the UK daily fibre intake. The soup was well accepted with few reports of adverse issues. Recruitment in this population is challenging, due to high levels of medication and ill health.
To examine the association between parenting styles and overall child dietary quality within households that are low-income and food-insecure.
Child dietary intake was measured via a 24 h dietary recall. Dietary quality was assessed using the Healthy Eating Index-2005 (HEI-2005). Parenting styles were measured and scored using the Parenting Styles and Dimensions Questionnaire. Linear regressions were used to test main and interaction associations between HEI-2005 scores and parenting styles.
Non-probability sample of low-income and food-insecure households in South Carolina, USA.
Parent–child dyads (n 171). Parents were ≥18 years old and children were 9–15 years old.
We found a significant interaction between authoritative and authoritarian parenting style scores. For those with a mean authoritarian score, each unit increase in authoritative score was associated with a higher HEI-2005 score (b = 3·36, P < 0.05). For those with an authoritarian score that was 1 sd above the mean authoritarian score, each unit increase in authoritative score was associated with a higher HEI-2005 score (b = 8.42, P < 0.01). For those with an authoritarian score that was −1 sd below the mean authoritarian score, each unit increase in authoritative score was associated with a lower HEI-2005 score; however, this was not significant (b = −1·69, P > 0·05). Permissive parenting style scores were negatively associated with child dietary quality (b = −2·79, P < 0·05).
Parenting styles should be considered an important variable that is associated with overall dietary quality in children living within low-income and food-insecure households.
Insomnia and depression are highly comorbid and mutually exacerbate clinical trajectories and outcomes. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces both insomnia and depression severity, and can be delivered digitally. This could substantially increase the accessibility to CBT-I, which could reduce the health disparities related to insomnia; however, the efficacy of digital CBT-I (dCBT-I) across a range of demographic groups has not yet been adequately examined. This randomized placebo-controlled trial examined the efficacy of dCBT-I in reducing both insomnia and depression across a wide range of demographic groups.
Of 1358 individuals with insomnia randomized, a final sample of 358 were retained in the dCBT-I condition and 300 in the online sleep education condition. Severity of insomnia and depression was examined as a dependent variable. Race, socioeconomic status (SES; household income and education), gender, and age were also tested as independent moderators of treatment effects.
The dCBT-I condition yielded greater reductions in both insomnia and depression severity than sleep education, with significantly higher rates of remission following treatment. Demographic variables (i.e. income, race, sex, age, education) were not significant moderators of the treatment effects, suggesting that dCBT-I is comparably efficacious across a wide range of demographic groups. Furthermore, while differences in attrition were found based on SES, attrition did not differ between white and black participants.
Results provide evidence that the wide dissemination of dCBT-I may effectively target both insomnia and comorbid depression across a wide spectrum of the population.
Extinction is the complete loss of a species, but the accuracy of that status depends on the overall information about the species. Dracaena umbraculifera was described in 1797 from a cultivated plant attributed to Mauritius, but repeated surveys failed to relocate it and it was categorized as Extinct on the IUCN Red List. However, several individuals labelled as D. umbraculifera grow in botanical gardens, suggesting that the species’ IUCN status may be inaccurate. The goal of this study was to understand (1) where D. umbraculifera originated, (2) which species are its close relatives, (3) whether it is extinct, and (4) the identity of the botanical garden accessions and whether they have conservation value. We sequenced a cpDNA region of Dracaena from Mauritius, botanical garden accessions labelled as D. umbraculifera, and individuals confirmed to be D. umbraculifera based on morphology, one of which is a living plant in a private garden. We included GenBank accessions of Dracaena from Madagascar and other locations and reconstructed the phylogeny using Bayesian and parsimony approaches. Phylogenies indicated that D. umbraculifera is more closely related to Dracaena reflexa from Madagascar than to Mauritian Dracaena. As anecdotal information indicated that the living D. umbraculifera originated from Madagascar, we conducted field expeditions there and located five wild populations; the species’ IUCN status should therefore be Critically Endangered because < 50 wild individuals remain. Although the identity of many botanical garden samples remains unresolved, this study highlights the importance of living collections for facilitating new discoveries and the importance of documenting and conserving the flora of Madagascar.
Silver Lake is the modern terminal playa of the Mojave River in southern California (USA). As a result, it is well located to record both influences from the winter precipitation dominated San Bernardino Mountains – the source of the Mojave River – and from the late summer to early fall North American monsoon at Silver Lake. Here, we present various physical, chemical and biological data from a new radiocarbon-dated, 8.2 m sediment core taken from Silver Lake that spans modern through 14.8 cal ka BP. Texturally, the core varies between sandy clay, clayey sand, and sand-silt-clay, often with abrupt sedimentological transitions. These grain-size changes are used to divide the core into six lake status intervals over the past 14.8 cal ka BP. Notable intervals include a dry Younger Dryas chronozone, a wet early Holocene terminating 7.8 – 7.4 cal ka BP, a distinct mid-Holocene arid interval, and a late Holocene return to ephemeral lake conditions. A comparison to potential climatic forcings implicates a combination of changing summer – winter insolation and tropical and N Pacific sea-surface temperature dynamics as the primary drivers of Holocene climate in the central Mojave Desert.
The histories of chronicles composed in England during the fourteenth and fifteenth centuries and onwards, with a focus on texts belonging to or engaging with the Prose Brut tradition, are thefocus of this volume. The contributors examine the composition, dissemination and reception of historical texts written in Anglo-Norman, Latin and English, including the Prose Brut chronicle (c. 1300 and later), Castleford's Chronicle (c. 1327), and Nicholas Trevet's Les Cronicles (c. 1334), looking at questions of the processes of writing, rewriting, printing and editing history. They cross traditional boundaries of subject and period, taking multi-disciplinary approaches to their studies in order to underscore the (shifting) historical, social and political contexts inwhich medieval English chronicles were used and read from the fourteenth century through to the present day. As such, the volume honours the pioneering work of the late Professor Lister M. Matheson, whose research in this area demonstrated that a full understanding of medieval historical literature demands attention to both the content of the works in question and to the material circumstances of producing those works.
Jaclyn Rajsic is a Lecturer in Medieval Literature in the School of English and Drama at Queen Mary University of London; Erik Kooper taught Old and Middle English at Utrecht University; until his retirement in 2007; Dominique Hoche is an Associate Professor at West Liberty University in West Virginia.
Contributors: Elizabeth J. Bryan, Caroline D. Eckhardt, A.S.G. Edwards, Dan Embree, Alexander L. Kaufman, Edward Donald Kennedy, Erik Kooper, Julia Marvin, William Marx, Krista A. Murchison, Heather Pagan, Jaclyn Rajsic, Christine M. Rose, NeilWeijer