Abstract Introduction We recently described a framework to quantify immune dysregulation in peripheral blood using cell-specific gene expression scores across the severity spectrum in sepsis (Moore et al, Nature Medicine). Given the associations between elevated neutrophil proportion in blood and bronchoalveolar lavage fluid and poor outcomes in idiopathic pulmonary fibrosis (IPF), we investigated whether the myeloid dysregulation score (MDS), which includes neutrophil-specific genes, generalizes to IPF and whether this differs depending on the collection technique. Methods We calculated the MDS at baseline in bulk RNA sequencing data from whole blood (containing all peripheral blood cells, including neutrophils) or peripheral blood mononuclear cell (PBMC) samples for 409 subjects (295 IPF patients, 114 healthy) in four publicly available IPF datasets (GSE93606, GSE33566, GSE38958, and GSE28042) and assigned high versus low myeloid dysregulation using median a threshold. We determined the difference in MDS between IPF patients and controls at baseline using Wilcoxon rank sum-test. When available, we assessed the correlation between forced vital capacity (FVC) and MDS using Spearman correlation. Using Kaplan-Meier estimator, we evaluated survival in cohorts with complete outcome information stratified by high versus low MDS. Results Of the 409 subjects, PBMCs or whole blood samples were available for 209 and 200 patients, respectively. 171 of 295 IPF patients had outcomes available. Of the combined 409 individuals in the four cohorts, MDS was significantly higher in IPF patients than healthy controls (p = 6.1e-06). This difference was significant in the whole blood cohort (p = 1.5 x 10-7) but not the PBMC cohort (p = 0.2). MDS was inversely correlated with baseline FVC (r = -0.1883, p = 0.026). In the whole blood cohort, transplant-free-survival within the first year was significantly higher for patients with low MDS than those with high MDS at baseline (HR = 4.4, 95% CI 1.4-14.0, p = 0.005), but not in the PBMC cohort (p > 0.9). Conclusion MDS in peripheral blood, which was derived predominantly in sepsis, is associated with severity and outcomes in IPF. The prognostic association is seen only in whole blood and not PBMCs, suggesting neutrophils may be associated with disease severity and outcomes in IPF. These results support shared immune dysregulation in sepsis and IPF that may contribute to disease trajectory in both conditions. This abstract is funded by: none

The opioid epidemic has affected Americans of all ages, social classes, and communities. Many different policies and programs have been implemented in the past with the overarching goal of minimizing the destructive impact of the opioid crisis. This paper examines factors that determine Americans' views on how their communities have been involved in the fight against the opioid epidemic, controlling for the perceived levels of substance use in the community, political affiliations, and demographic factors. Data came from an AP-NORC poll (Pharmaceutical companies and drug users most often blamed for opioid crisis) conducted in April 2019. Results show the complexity and the multifaceted nature of the opioid crisis. Binary logistic analysis was used. While different factors significantly explain the assessments of community members, depending on the policy being used, some factors consistently significantly explain their views regardless of the policy. Overall, results indicate that different opinions are shared depending on Americans' political, residential, and social characteristics as well as the community exposure to substance use. Several policy recommendations are made. This study adds to the body of literature on the opioid crisis and communities' assessment of what has been done to help stop the crisis.

Rationale: Idiopathic pulmonary fibrosis (IPF) causes irreversible fibrosis of the lung parenchyma. Although antifibrotic therapy can slow IPF progression, treatment response is variable. There exists a critical need to develop a precision medicine approach to IPF. Objectives: To identify and validate biologically driven molecular endotypes of IPF. Methods: Latent class analysis (LCA) was independently performed in prospectively recruited discovery (n = 875) and validation (n = 347) cohorts. Twenty-five plasma biomarkers associated with fibrogenesis served as class-defining variables. The association between molecular endotype and 4-year transplant-free survival was tested using multivariable Cox regression adjusted for baseline confounders. Endotype-dependent differential treatment response to future antifibrotic exposure was then assessed in a pooled cohort of patients naive to antifibrotic therapy at the time of biomarker measurement (n = 555). Measurements and Main Results: LCA independently identified two latent classes in both cohorts (P < 0.0001). WFDC2 (WAP four-disulfide core domain protein 2) was the most important determinant of class membership across cohorts. Membership in class 2 was characterized by higher biomarker concentrations and a higher risk of death or transplant (discovery, hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.64-2.48; P < 0.001; validation, HR, 1.95; 95% CI, 1.34-2.82; P < 0.001). In pooled analysis, significant heterogeneity in treatment effect was observed between endotypes (P = 0.030 for interaction), with a favorable antifibrotic response in class 2 (HR, 0.64; 95% CI, 0.45-0.93; P = 0.018) but not in class 1 (HR, 1.19; 95% CI, 0.77-1.84; P = 0.422). Conclusions: In this multicohort study, we identified two novel molecular endotypes of IPF with divergent clinical outcomes and responses to antifibrotic therapy. Pending further validation, these endotypes could enable a precision medicine approach for future IPF clinical trials.

This study examined attitudes toward pre-exposure prophylaxis (PrEP) and medical decision making about PrEP uptake among educated young Ghanaians in Lower Manya Krobo Municipality (LMKM) to prevent HIV/AIDS. Lower Manya Krobo Municipality has a history of high HIV infection. There is paucity of studies on attitudes towards and medical decisions on PrEP among Ghanaians. PrEP is currently not approved in Ghana and West Africa generally. Efforts are, however, being made to study the possible use of the intervention in Ghana, against a background of generalized HIV infection, and increasing infection among the youth. We used primary data administered through mostly closed-ended questionnaires to 261 respondents. A quasi-experimental one group study was adopted. Respondents were asked the same questions on attitudes towards and medical decisions on PrEP before and after watching a six-minute YouTube video on PrEP. ANOVA was used to examine statistical significance between the paired, pre-and-post data. The Wilcoxon signed rank test helped with conclusions about the mean difference between the paired responses. The findings corroborated with previous literature regarding high sexual risk among the young people. There was a statistically significant effect of the video on attitudes and medical decisions regarding use of PrEP. It seemed that if PrEP were available, the study participants would uptake it to proactively protect themselves from HIV infection. They also had a higher inclination of using PrEP if a medical officer recommended its use, and its side effects were minimal. Statistically significant gendered differences showed that female respondents were less concerned about being stigmatized as having HIV if they took PrEP and were also more likely to respond favorably to the recommendation of a physician to use the intervention, compared to their male counterparts. Public education on PrEP use should consider the involvement of a medical figure.

Abstract Recovery from substance use is generally a lifelong process with different pathways. This study used data from the Justice Community Opioid Innovation Network (JCOIN), 2021, a nationally representative survey of over 6,000 American adults, to examine factors that influence the views on most helpful pathways for recovery among older Americans (60 years and older) compared to their younger counterparts (less than 60 years old). Multiple linear regression was used to determine differences across age, political affiliation, cultural identity, and regional location. A factor analysis of 9 questions that asked respondents to rate the most helpful pathways for recovery generated three domains: 1. Medical services enabling environment (PCP, intensive inpatient program, and rehab program); 2. Direct conventional treatment (Prescription medication and therapist); and 3. Sociocultural factors/non-conventional treatment (Family/friends, spiritual/natural healer, self-help group, and faith-based organization). Older and younger Democrats, Independents, and residents of the Northeast and Midwest regions agreed that the medical services were helpful for recovery. While younger and older Democrats believed that direct conventional treatment was helpful, younger and older Republics as well as younger married people believed it to be less helpful. While older Democrats agreed that non-conventional treatments are most helpful, younger Democrats and Independents believed them to be less helpful. However, younger Republicans, Blacks and Hispanics believed that they are most helpful. Given the significant differences in the views of older and younger Americans on helpful pathways to recovery, policymakers and stakeholders are encouraged to be mindful of the several policy recommendations presented in the paper.

This article reports on a study that examined the lived experience of 15 foreign-born female university faculty members through the qualitative research methodology called photo elicitation. The article investigates ways in which intersectionality, social marginality, and resilience offer a framework for understanding the participants’ lived experiences of being foreign-born, female, and academic in the United States. Findings demonstrate that as non-native-born women, the faculty members faced multi-faceted challenges in both personal and professional realms. Implications for the role of social work advocacy and higher education policy advocacy are discussed.

OBJECTIVES To examine factors that account for disparities in cancer clinical trial participation. SAMPLE & SETTING Pooled data from Behavioral Risk Factor Surveillance System surveys between 2010 and 2017. METHODS & VARIABLES Univariate and binary logistic regression analyses were used to examine the associations between participation in clinical trials and demographic and health characteristics, using SAS® procedures to account for complex sample features. RESULTS Univariate analyses showed that age, race, income, and self-rated health status were significantly associated with the likelihood of participating in cancer clinical trials. Binary logistic analyses showed that Black respondents who were ever diagnosed with cancer were more likely to participate in cancer clinical trials relative to White counterparts. Respondents aged 50-64 years were more likely to have participated in cancer clinical trials compared to those aged 65 years or older. However, respondents who self-rated their health as excellent or very good were less likely to participate in cancer clinical trials. IMPLICATIONS FOR NURSING Involving properly trained nurses and nurse practitioners from diverse backgrounds in cancer clinical trials to inform people with cancer about trials and ways to reduce personal barriers will increase participation from all people, regardless of socioeconomic and demographic characteristics.