Longitudinal Associations Between MicroRNAs and Weight in the Diabetes Prevention Program.

OBJECTIVE: Circulating microRNAs show cross-sectional associations with overweight and obesity. Few studies provided data to differentiate between a snapshot perspective on these associations versus how microRNAs characterize prodromal risk from disease pathology and complications. This study assessed longitudinal relationships between circulating microRNAs and weight at multiple time-points in the Diabetes Prevention Program trial. RESEARCH DESIGN AND METHODS: A subset of participants (n=150) from the Diabetes Prevention Program were included. MicroRNAs were measured from banked plasma using a Fireplex Assay. We used generalized linear mixed models to evaluate relationships between microRNAs and changes in weight at baseline, year-1, and year-2. Logistic regression was used to evaluate whether microRNAs at baseline were associated with weight change after 2 years. RESULTS: In fully adjusted models that included relevant covariates, seven miRs (i.e., miR-126, miR-15a, miR-192, miR-23a, and miR-27a) were statistically associated with weight over 2 years. MiR-197 and miR-320a remained significant after adjustment for multiple comparisons. Baseline levels of let-7f, miR-17, and miR-320c were significantly associated with 3% weight loss after 2 years in fully adjusted models. DISCUSSION: This study provided evidence for longitudinal relationships between circulating microRNAs and weight. Because microRNAs characterize the combined effects of genetic determinants and responses to behavioral determinants, they may provide insights about the etiology of overweight and obesity in the context or risk for common, complex diseases. Additional studies are needed to validate the potential genes and biological pathways that might be targeted by these microRNA biomarkers and have mechanistic implications for weight loss and disease prevention.

MicroRNAs Associated with Metformin Treatment in the Diabetes Prevention Program.

The Diabetes Prevention Program (DPP) randomized controlled trial demonstrated that metformin treatment reduced progression to type 2 diabetes (T2D) by 31% compared to placebo in adults with prediabetes. Circulating micro-ribonucleic acids (miRs) are promising biomarkers of T2D risk, but little is known about their associations with metformin regimens for T2D risk reduction. We compared the change in 24 circulating miRs from baseline to 2 years in a subset from DPP metformin intervention (n = 50) and placebo (n = 50) groups using Wilcoxon signed rank tests. Spearman correlations were used to evaluate associations between miR change and baseline clinical characteristics. Multiple linear regression was used to adjust for covariates. The sample was 73% female, 17% Black, 13% Hispanic, and 50 ± 11 years. Participants were obese, normotensive, prediabetic, and dyslipidemic. Change in 12 miR levels from baseline to 2 years was significantly different in the metformin group compared with placebo after adjusting for multiple comparisons: six (let-7c-5p, miR-151a-3p, miR-17-5p, miR-20b-5p, miR-29b-3p, and miR-93-5p) were significantly upregulated and six (miR-130b-3p, miR-22-3p, miR-222-3p, miR-320a-3p, miR-320c, miR-92a-3p) were significantly downregulated in the metformin group. These miRs help to explain how metformin is linked to T2D risk reduction, which may lead to novel biomarkers, therapeutics, and precision health strategies.

Intraphagosomal Free Ca2+ Changes during Phagocytosis.

Phagocytosis (and endocytosis) is an unusual cellular process that results in the formation of a novel subcellular organelle, the phagosome. This phagosome contains not only the internalised target of phagocytosis but also the external medium, creating a new border between extracellular and intracellular environments. The boundary at the plasma membrane is, of course, tightly controlled and exploited in ionic cell signalling events. Although there has been much work on the control of phagocytosis by ions, notably, Ca2+ ions influxing across the plasma membrane, increasing our understanding of the mechanism enormously, very little work has been done exploring the phagosome/cytosol boundary. In this paper, we explored the changes in the intra-phagosomal Ca2+ ion content that occur during phagocytosis and phagosome formation in human neutrophils. Measuring Ca2+ ion concentration in the phagosome is potentially prone to artefacts as the intra-phagosomal environment experiences changes in pH and oxidation. However, by excluding such artefacts, we conclude that there are open Ca2+ channels on the phagosome that allow Ca2+ ions to "drain" into the surrounding cytosol. This conclusion was confirmed by monitoring the translocation of the intracellularly expressed YFP-tagged C2 domain of PKC-γ. This approach marked regions of membrane at which Ca2+ influx occurred, the earliest being the phagocytic cup, and then the whole cell. This paper therefore presents data that have novel implications for understanding phagocytic Ca2+ signalling events, such as peri-phagosomal Ca2+ hotspots, and other phenomena.

An Exploratory Analysis of Contributors to Cognitive Functioning Among Sexual and Gender Minority Individuals Who Had COVID-19.

Sexual and gender minority (SGM) individuals face mental health disparities. However, research analyzing SGM people's mental health after a COVID-19 diagnosis is scarce. In this secondary analysis of a remote study, we 1) examined associations between cognitive and psychosocial health and 2) explored differences between these health outcomes among SGM (n = 14) and heterosexual cisgender (n = 64) U.S. adults who had COVID-19. We used the Patient Reported Outcome Measures Information System (PROMIS) v2.0 to assess subjective cognition and the BrainCheck cognitive test to analyze objective cognition. We administered the Perceived Stress Scale and PROMIS 57 Profile V.2.0 to measure psychosocial health. SGM COVID-19 survivors had worse scores in depression, anxiety, sleep disturbance, pain, stress, and objective cognition than heterosexual cisgender participants (p-values < .05). Objective cognition was associated with age, SGM classification, racial or ethnic minority classification, income, comorbidities, COVID-19 severity, number of symptoms, and pain (|0.137| < r < |0.373|, p-values < .05). Subjective cognition was associated with comorbidities, number of symptoms, depression, anxiety, sleep disturbance, pain, and stress (|0.158| < r < |0.537|, p-values < .05). Additional studies are needed to expand what is known about post-COVID-19 health disparities and to guide policies and interventions that promote cognitive functioning.

MicroRNAs Associated with Metformin Treatment in the Diabetes Prevention Program.

The Diabetes Prevention Program (DPP) randomized controlled trial demonstrated that metformin treatment reduced progression to type 2 diabetes (T2D) by 31% compared to placebo in adults with prediabetes. Circulating micro-ribonucleic acids (miRs) are promising biomarkers of T2D risk, but little is known about their associations with metformin regimens for T2D risk reduction. We compared the change in 24 circulating miRs from baseline to 2 years in a subset from DPP metformin intervention (n = 50) and placebo (n = 50) groups using Wilcoxon signed rank tests. Spearman's correlations were used to evaluate associations between miR change and baseline clinical characteristics. Multiple linear regression was used to adjust for covariates. The sample was 73% female, 17% Black, 13% Hispanic, and 50 ± 11 years. Participants were obese, normotensive, prediabetic, and dyslipidemic. Change in 12 miR levels from baseline to 2 years was significantly different in the metformin group compared with placebo after adjusting for multiple comparisons: six (let-7c-5p, miR-151a-3p, miR-17-5p, miR-20b-5p, miR-29b-3p, and miR-93-5p) were significantly upregulated and six (miR-130b-3p, miR-22-3p, miR-222-3p, miR-320a-3p, miR-320c, miR-92a-3p) were significantly downregulated in the metformin group. These miRs help to explain how metformin is linked to T2D risk reduction, which may lead to novel biomarkers, therapeutics, and precision-health strategies.

Multi-Tiered Assessment of Gene Expression Provides Evidence for Mechanisms That Underlie Risk for Type 2 Diabetes.

Introduction: Integrated transcriptome and microRNA differential gene expression (DEG) analyses may help to explain type 2 diabetes (T2D) pathogenesis in at-risk populations. The purpose of this study was to characterize DEG in banked biospecimens from underactive adult participants who responded to a randomized clinical trial measuring the effects of lifestyle interventions on T2D risk factors. DEGs were further examined within the context of annotated biological pathways. Methods: Participants (n = 52) in a previously completed clinical trial that assessed a 12-week behavioural intervention for T2D risk reduction were included. Participants who showed >6mg/dL decrease in fasting blood glucose were identified as responders. Gene expression was measured by RNASeq, and overrepresentation analysis within KEGG pathways and weighted gene correlation network analysis (WGCNA) were performed. Results: No genes remained significantly differentially expressed after correction for multiple comparisons. One module derived by WGCNA related to body mass index was identified, which contained genes located in KEGG pathways related to known mechanisms underlying risk for T2D as well as pathways related to neurodegeneration and protein misfolding. A network analysis showed indirect connections between genes in this module and islet amyloid polypeptide (IAPP), which has previously been hypothesized as a mechanism for T2D. Discussion: We validated prior studies that showed pathways related to metabolism, inflammation/immunity, and endocrine/hormone function are related to risk for T2D. We identified evidence for new potential mechanisms that include protein misfolding. Additional studies are needed to determine whether these are potential therapeutic targets to decrease risk for T2D.

A sum of its parts: A systematic review evaluating biopsychosocial and behavioral determinants of perinatal depression.

Introduction: Depression is one of the most common yet underdiagnosed perinatal complications and our understanding of the pathophysiology remains limited. Though perinatal depression is considered to have a multifactorial etiology, integrative approaches to investigation are minimal. This review takes an integrative approach to systematically evaluate determinants and potential interactions among determinants of perinatal depression across four domains (i.e., biological, behavioral, environmental, social) and appraise the quality of methods applied. Methods: Four databases (i.e., PubMed, CINAHL, APA PsycInfo, and Web of Science) were systematically searched to identify studies examining determinants of perinatal depression in adult perinatal persons (≥ 18 years). Articles were excluded if the outcomes were not focused on perinatal persons and depression or depression symptoms, the evaluation of depression was specific to a discrete facet of the perinatal period with probable psychological consequences (e.g., abortion, fetal/infant loss, adoption), or was considered grey literature. The Critical Appraisal Skills Programme and AXIS tools were used to guide and standardize quality appraisal assessments and determine the level of risk of bias. Results: Of the 454 articles identified, 25 articles were included for final review. A total of 14 categories of determinants were investigated: biological (5), behavioral (4), social and environmental (5). Though only 28% of studies simultaneously considered determinants under more than one domain, a pattern of interactions with the tryptophan pathway emerged when determinants across domains were aggregated. Concerns for risk of bias were noted or were unclear for three types of bias: 13 (52%) selection bias, 3 (12%) recall bias, and 24 (96%) measurement bias. Conclusions: Future research is needed to explore interactions among determinants and the tryptophan pathway; to strengthen the methods applied to this area of inquiry; and to generate evidence for best practices in reporting, selecting, and applying methods for measuring determinants and perinatal depression.

Cancer-related cognitive impairment in racial and ethnic minority groups: a scoping review.

PURPOSE: Disparities in cognitive function among racial and ethnic groups have been reported in non-cancer conditions, but cancer-related cognitive impairment (CRCI) in racial and ethnic minority groups is poorly understood. We aimed to synthesize and characterize the available literature about CRCI in racial and ethnic minority populations. METHODS: We conducted a scoping review in the PubMed, PsycInfo, and Cumulative Index to Nursing and Allied Health Literature databases. Articles were included if they were published in English or Spanish, reported cognitive functioning in adults diagnosed with cancer, and characterized the race or ethnicity of the participants. Literature reviews, commentaries, letters to the editor, and gray literature were excluded. RESULTS: Seventy-four articles met the inclusion criteria, but only 33.8% differentiated the CRCI findings by racial or ethnic subgroups. There were associations between cognitive outcomes and the participants' race or ethnicity. Additionally, some studies found that Black and non-white individuals with cancer were more likely to experience CRCI than their white counterparts. Biological, sociocultural, and instrumentation factors were associated with CRCI differences between racial and ethnic groups. CONCLUSIONS: Our findings indicate that racial and ethnic minoritized individuals  may be disparately affected by CRCI. Future research should use standardized guidelines for measuring and reporting the self-identified racial and ethnic composition of the sample; differentiate CRCI findings by racial and ethnic subgroups; consider the influence of structural racism in health outcomes; and develop strategies to promote the participation of members of racial and ethnic minority groups.

Review of databases for experimentally validated human microRNA-mRNA interactions.

MicroRNAs (miRs) may contribute to disease etiology by influencing gene expression. Numerous databases are available for miR target prediction and validation, but their functionality is varied, and outputs are not standardized. The purpose of this review is to identify and describe databases for cataloging validated miR targets. Using Tools4miRs and PubMed, we identified databases with experimentally validated targets, human data, and a focus on miR-messenger RNA (mRNA) interactions. Data were extracted about the number of times each database was cited, the number of miRs, the target genes, the interactions per database, experimental methodology and key features of each database. The search yielded 10 databases, which in order of most cited to least were: miRTarBase, starBase/The Encyclopedia of RNA Interactomes, DIANA-TarBase, miRWalk, miRecords, miRGator, miRSystem, miRGate, miRSel and targetHub. Findings from this review suggest that the information presented within miR target validation databases can be enhanced by adding features such as flexibility in performing queries in multiple ways, downloadable data, ongoing updates and integrating tools for further miR-mRNA target interaction analysis. This review is designed to aid researchers, especially those new to miR bioinformatics tools, in database selection and to offer considerations for future development and upkeep of validation tools. Database URL http://mirtarbase.cuhk.edu.cn/.

Pandemic perspectives from the frontline-The nursing stories.

AIM: To describe the experiences of registered nurses working in a US healthcare system during the COVID-19 pandemic. DESIGN: This qualitative thematic analysis study is a secondary analysis of stories submitted by nurses to a repository established by the parent study. METHODS: Registered nurses working in various roles in a healthcare system submitted stories (N = 45) to open-ended prompts via an online repository between June 2020 and February 2021. A team of three nurse scientists coded the stories using Dedoose software. Initial codes were then reviewed by the team to synthesize initial coding into themes. The COREQ checklist was used to ensure research reporting guidelines were met. RESULTS: Thematic analysis revealed three themes in a global theme of COVID-19 pandemic-related personal and professional evolution: (1) The art and science of pandemic nursing, (2) Persisting despite challenges; and (3) Learning as we went. Each of the three organizing themes were supported by basic themes. CONCLUSIONS: Identified themes affirm some of nursing's long-standing core values, such as the central role of human connectedness in restoring health, but findings also reflect new evolutionary processes of moral identity formation that occurred among nurses and the nursing profession during the COVID-19 pandemic. IMPACT: Findings from this study describe the processes by which nurses' moral identity evolved during a segment of the COVID-19 pandemic. Collectively, these evolutions represent important shifts in the nursing profession. Using findings from this study, nurse educators, nurse managers and healthcare administrators will be able to implement effective, sustainable policies and processes that meet the needs of both the community and the workforce. NO PATIENT OR PUBLIC CONTRIBUTION: This study was designed to capture the experiences of nurses employed by one healthcare organization. However, it was not conducted using input or suggestions from the public or the patient population served by the organization.

Cognitive Impairment in Non-critical, Mild-to-Moderate COVID-19 Survivors.

IMPORTANCE: Previous studies of post-acute COVID-19 syndrome have focused on critical cases with severe disease. However, most cases are mild to moderate in disease severity. OBJECTIVE: We aimed to examine cognitive outcomes in cases of non-critical, mild-to-moderate COVID-19. Design, Setting, and Participants: In this cross-sectional study, we enrolled 72 adults aged 22 to 65 years in Central Texas who had non-critical, mild-to-moderate COVID-19 infection between 13 January 2021 and 20 April 2021. MAIN OUTCOMES AND MEASURES: We remotely administered cognitive-behavioral testing to determine the frequency of cognitive impairment and examine demographic, clinical, and psychosocial contributors to impairment. RESULTS: The frequency of objective cognitive impairment was 40%. The largest number of participants (24%) showed impairment on a measure of executive functioning. Attention and processing speed was more impaired in males (OR = 1.5, 95%CI = 0.23-2.9). Males endorsed lower adherence to social distancing guidelines (U = 590, p = 0.01), which was in turn associated with cognitive impairment across participants (r = -0.30, p = 0.01). Younger age was correlated with impairment (r = -0.26, p = 0.03) but was also associated with racial/ethnic minority status (r = -0.31, p = 0.01) and increased psychological symptoms (p < 0.04). Greater number of COVID-19 symptoms was correlated with lower subjective cognitive function (r = -0.38, p = 0.001) as well as psychosocial function (r > 0.24, p < 0.05). Moderate COVID-19 severity was associated with attention/processing speed impairment (r = 0.27, p = 0.03), increased pain (r = 0.31, p = 0.01), and higher number of COVID-19 symptoms (r = 0.32, p = 0.01). CONCLUSION AND RELEVANCE: Mild or moderate COVID-19 infection may be associated with cognitive impairments, especially in the domain of executive functioning. A subgroup of younger individuals may be more vulnerable to cognitive and psychosocial effects of COVID-19. HIGHLIGHTS: Question: How frequent is cognitive impairment among non-critical, mild-to-moderate COVID-19 survivors? FINDINGS: In this cross-sectional study of 72 adults, 40% demonstrated cognitive impairment, particularly in executive function. MEANING: Neurologic sequelae, such as cognitive impairment, may be common following COVID-19 infection.

Serine, N-acetylaspartate differentiate adolescents with juvenile idiopathic arthritis compared with healthy controls: a metabolomics cross-sectional study.

BACKGROUND: In comparison with the general population, adolescents with juvenile idiopathic arthritis (JIA) are at higher risk for morbidity and mortality. However, limited evidence is available about this condition's underlying metabolic profile in adolescents with JIA relative to healthy controls. In this untargeted, cross-sectional metabolomics study, we explore the plasma metabolites in this population. METHODS: A sample of 20 adolescents with JIA and 20 controls aged 13-17 years were recruited to complete surveys, provide medical histories and biospecimens, and undergo assessments. Fasting morning plasma samples were processed with liquid chromatography-mass spectrometry. Data were centered, scaled, and analyzed using generalized linear models accounting for age, sex, and medications (p-values adjusted for multiple comparisons using the Holm method). Spearman's correlations were used to evaluate relationships among metabolites, time since diagnosis, and disease severity. RESULTS: Of 72 metabolites identified in the samples, 55 were common to both groups. After adjustments, 6 metabolites remained significantly different between groups. Alpha-glucose, alpha-ketoglutarate, serine, and N-acetylaspartate were significantly lower in the JIA group than in controls; glycine and cystine were higher. Seven additional metabolites were detected only in the JIA group; 10 additional metabolites were detected only in the control group. Metabolites were unrelated to disease severity or time since diagnosis. CONCLUSIONS: The metabolic signature of adolescents with JIA relative to controls reflects a disruption in oxidative stress; neurological health; and amino acid, caffeine, and energy metabolism pathways. Serine and N-acetylaspartate were promising potential biomarkers, and their metabolic pathways are linked to both JIA and cardiovascular disease risk. The pathways may be a source of new diagnostic, treatment, or prevention options. This study's findings contribute new knowledge for systems biology and precision health approaches to JIA research. Further research is warranted to confirm these findings in a larger sample.

Describing cognitive function and psychosocial outcomes of COVID-19 survivors: A cross-sectional analysis.

BACKGROUND: Neurological and psychological symptoms are increasingly realized in the post-acute phase of COVID-19. PURPOSE: To examine and characterize cognitive and related psychosocial symptoms in adults (21-75 years) who tested positive for or were treated as positive for COVID-19. METHODS: In this cross-sectional study, data collection included a cognitive testing battery (Trails B; Digit Symbol; Stroop; Immediate and Delayed Verbal Learning) and surveys (demographic/clinical history; self-reported cognitive functioning depressive symptoms, fatigue, anxiety, sleep disturbance, social role performance, and stress). Results were compared with published norms, rates of deficits (more than 1 standard deviation (SD) from the norm) were described, and correlations were explored. RESULTS: We enrolled 52 participants (mean age 37.33 years; 78.85% female) who were, on average, 4 months post illness. The majority had a history of mild or moderate COVID-19 severity. Forty percent of participants demonstrated scores that were 1 SD or more below the population norm on one or more of the cognitive tests. A subset had greater anxiety (21.15%), depressive symptoms (23.07%), and sleep disturbance (19.23%) than population norms. Age differences were identified in Stroop, Digit Symbol, and Trails B scores by quartile ( p < .01), with worse performance in those 28-33 years old. CONCLUSIONS: Cognitive dysfunction and psychological symptoms may be present in the weeks or months after COVID-19 diagnosis, even in those with mild to moderate illness severity. IMPLICATIONS FOR PRACTICE: Clinicians need to be aware and educate patients about the potential late/long-term cognitive and psychological effects of COVID-19, even in mild to moderate disease.

Caring for sick kids: An integrative review of the evidence about the prevalence of compassion fatigue and effects on pediatric nurse retention.

PROBLEM: Compassion Fatigue (CF) in healthcare professionals has been explored in multiple studies, but few focused on hospital-based pediatric nurses. The purpose of this integrative review is to synthesize the evidence about CF prevalence in nurses caring for pediatric patients, and to describe its effects on retention and job satisfaction. ELIGIBILITY CRITERIA: Included studies were in English from any date describing research or quality improvement studies about CF in pediatric nurses. SAMPLE: An integrative review of nine electronic databases yielded 13 articles about 1921 nurses. Data were synthesized from four qualitative and nine quantitative studies separately before integrating results. A risk of bias analysis was included for evidence level and quality. RESULTS: Overall CF prevalence was low, but 14% of nurses were at high risk of burnout and 10% were at high risk for secondary traumatic stress. Studies examining the effects of CF on retention found no significant relationship. Most studies were about critical care or oncology nurses. CONCLUSIONS: A subset of pediatric nurses is highly vulnerable to CF, but more high-quality evidence is needed to fully address this topic. Leaders should study CF prevalence, protective and exacerbating factors, relationships between CF and retention, and targeted strategies to resolve CF in high-risk nurses.

Systematic review of transcriptome and microRNAome associations with gestational diabetes mellitus.

Purpose: Gestational diabetes (GDM) is associated with increased risk for preterm birth and related complications for both the pregnant person and newborn. Changes in gene expression have the potential to characterize complex interactions between genetic and behavioral/environmental risk factors for GDM. Our goal was to summarize the state of the science about changes in gene expression and GDM. Design: The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods: PubMed articles about humans, in English, from any date were included if they described mRNA transcriptome or microRNA findings from blood samples in adults with GDM compared with adults without GDM. Results: Sixteen articles were found representing 1355 adults (n=674 with GDM, n=681 controls) from 12 countries. Three studies reported transcriptome results and thirteen reported microRNA findings. Identified pathways described various aspects of diabetes pathogenesis, including glucose and insulin signaling, regulation, and transport; natural killer cell mediated cytotoxicity; and fatty acid biosynthesis and metabolism. Studies described 135 unique miRNAs that were associated with GDM, of which eight (miR-16-5p, miR-17-5p, miR-20a-5p, miR-29a-3p, miR-195-5p, miR-222-3p, miR-210-3p, and miR-342-3p) were described in 2 or more studies. Findings suggest that miRNA levels vary based on the time in pregnancy when GDM develops, the time point at which they were measured, sex assigned at birth of the offspring, and both the pre-pregnancy and gestational body mass index of the pregnant person. Conclusions: The mRNA, miRNA, gene targets, and pathways identified in this review contribute to our understanding of GDM pathogenesis; however, further research is warranted to validate previous findings. In particular, longitudinal repeated-measures designs are needed that control for participant characteristics (e.g., weight), use standardized data collection methods and analysis tools, and are sufficiently powered to detect differences between subgroups. Findings may be used to improve early diagnosis, prevention, medication choice and/or clinical treatment of patients with GDM.

Best practices for recruitment of adolescents for biobanking and precision health research: a retrospective analysis comparing juvenile idiopathic arthritis cases with healthy controls.

BACKGROUND: Precision health in adolescents relies on the successful collection of data and biospecimens from an adequately sized sample of cases and comparison group(s), often healthy controls, to answer the research question. This research report describes the recruitment strategy, enrollment rates, and approach utilized in a successful biobehavioral research study. The study was designed to examine key health indicators in adolescents (13-17 years of age) with juvenile idiopathic arthritis (JIA) compared to a control group of healthy adolescents. The purpose of this analysis is to establish best practices and identify strategies to overcome barriers to recruitment of older adolescents, an age group that tends to be underrepresented in research studies. METHODS: A retrospective secondary analysis of data from a parent study about JIA with high consent rates was employed to explore factors affecting enrollment into the biobehavioral study. RESULTS: Of the 113 subjects who were recruited to the study, 74 met the eligibility criteria and reviewed the consent form. The consented group (n=40) represents 54% of those who were eligible upon initial screening. The rate of project enrollment was 2.7 participants per month. The pediatric rheumatologists referred 85% of the JIA group, and the study's principal investigator, a nurse scientist, referred 95% of the control group. Typical recruitment strategies, such as posting on social media, distributing flyers, and cold-calling potential participants from the clinic schedule were ineffective for both cases and controls. Barriers to enrollment included scheduling and fear of venipuncture. There were no demographic characteristics that significantly explained enrollment, differentiating between those who agreed to participate compared to those who refused. Successful strategies for enrollment of adolescents into this biobehavioral research study included scheduling study visits on weekends and school holidays; an informed consent and assent process that addressed adolescent fears of venipuncture; including a JIA patient on the study team; and utilizing existing relationships to maximize enrollment efforts. CONCLUSIONS: Effective recruitment and enrollment practices were relationship-specific and patient-centered. Researchers should utilize best practices to ensure that precision health for adolescents is advanced.

Exploring the Career Engagement, Interests, and Goals of Pharmacy Students Identifying as Underrepresented Racial Minorities.

Objective. To examine pharmacy career engagement, interest, and confidence in Doctor of Pharmacy (PharmD) students identifying as underrepresented racial minorities (URMs).Methods. A 15-item survey about career engagement, confidence, and goals was administered at a business session of a national conference. The survey included demographic items and items about career exposure prior to and during school, career aspirations after graduation, frequency of engagement in various settings, career factors, and career confidence. Cronbach alpha was used to examine survey reliability. Descriptive statistics and nonparametric statistical tests were used to analyze survey responses.Results. Sixty-nine URM students completed the survey. Most indicated frequent engagement with community pharmacy prior to and during school; no engagement with hospital pharmacy prior to school, yet occasional or frequent engagement during school; and no engagement with the pharmaceutical industry prior to and during school. Most selected hospital pharmacy as their career aspiration, followed by community pharmacy and industry. Approximately half indicated an interest in completing a postgraduate fellowship. Items selected as important to career choice included patient care, job security, and level of stress. Group differences were found by gender and year in school.Conclusion. Despite calls for diversity in pharmacy, there is a paucity of research in this area. This study provides a first glimpse into the career engagement, confidence, and goals of students identifying as URMs, raising a number of critical issues for pharmacy education. Moving forward, schools, employers, and researchers must work to better understand the career development of URM students, including barriers and facilitators to access and success.

Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis.

PURPOSE: Corticosteroids are now recommended for patients with severe COVID-19 including those with COVID-related ARDS. This has generated renewed interest regarding whether corticosteroids should be used in non-COVID ARDS as well. The objective of this study was to summarize all RCTs examining the use of corticosteroids in ARDS. METHODS: The protocol of this study was pre-registered on PROSPERO (CRD42020200659). We searched online databases including MEDLINE, EMBASE, CDC library of COVID research, CINAHL, and COCHRANE. We included RCTs that compared the effect of corticosteroids to placebo or usual care in adult patients with ARDS, including patients with COVID-19. Three reviewers abstracted data independently and in duplicate using a pre-specified standardized form. We assessed individual study risk of bias using the revised Cochrane ROB-2 tool and rated certainty in outcomes using GRADE methodology. We pooled data using a random effects model. The main outcome for this review was 28-day-mortality. RESULTS: We included 18 RCTs enrolling 2826 patients. The use of corticosteroids probably reduced mortality in patients with ARDS of any etiology (2740 patients in 16 trials, RR 0.82, 95% CI 0.72-0.95, ARR 8.0%, 95% CI 2.2-12.5%, moderate certainty). Patients who received a longer course of corticosteroids (over 7 days) had higher rates of survival compared to a shorter course. CONCLUSION: The use of corticosteroids probably reduces mortality in patients with ARDS. This effect was consistent between patients with COVID-19 and non-COVID-19 ARDS, corticosteroid types, and dosage.