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Single-nucleus sequencing reveals enriched expression of genetic risk factors in extratelencephalic neurons sensitive to degeneration in ALS

Limone, Francesco; Mordes, Daniel A; Couto, Alexander; Joseph, Brian J; Mitchell, Jana M; Therrien, Martine; Ghosh, Sulagna Dia; Meyer, Daniel; Zhang, Yingying; Goldman, Melissa; Bortolin, Laura; Cobos, Inma; Stevens, Beth; McCarroll, Steven A; Kadiu, Irena; Burberry, Aaron; Pietiläinen, Olli; Eggan, Kevin
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive loss of motor function linked to degenerating extratelencephalic neurons/Betz cells (ETNs). The reasons why these neurons are selectively affected remain unclear. Here, to understand the unique molecular properties that may sensitize ETNs to ALS, we performed RNA sequencing of 79,169 single nuclei from cortices of patients and controls. In both patients and unaffected individuals, we found significantly higher expression of ALS risk genes in THY1+ ETNs, regardless of diagnosis. In patients, this was accompanied by the induction of genes involved in protein homeostasis and stress responses that were significantly induced in a wide collection of ETNs. Examination of oligodendroglial and microglial nuclei revealed patient-specific downregulation of myelinating genes in oligodendrocytes and upregulation of an endolysosomal reactive state in microglia. Our findings suggest that selective vulnerability of extratelencephalic neurons is partly connected to their intrinsic molecular properties sensitizing them to genetics and mechanisms of degeneration.
PMID: 38907103
ISSN: 2662-8465
CID: 5672512

Limited Evidence of Shared Decision Making for Prostate Cancer Screening in Audio-Recorded Primary Care Visits Among Black Men and their Healthcare Providers

Stevens, Elizabeth R; Thomas, Jerry; Martinez-Lopez, Natalia; Fagerlin, Angela; Ciprut, Shannon; Shedlin, Michele; Gold, Heather T; Li, Huilin; Davis, J Kelly; Campagna, Ada; Bhat, Sandeep; Warren, Rueben; Ubel, Peter; Ravenell, Joseph E; Makarov, Danil V
Prostate-specific antigen (PSA)-based prostate cancer screening is a preference-sensitive decision for which experts recommend a shared decision making (SDM) approach. This study aimed to examine PSA screening SDM in primary care. Methods included qualitative analysis of audio-recorded patient-provider interactions supplemented by quantitative description. Participants included 5 clinic providers and 13 patients who were: (1) 40-69 years old, (2) Black, (3) male, and (4) attending clinic for routine primary care. Main measures were SDM element themes and "observing patient involvement in decision making" (OPTION) scoring. Some discussions addressed advantages, disadvantages, and/or scientific uncertainty of screening, however, few patients received all SDM elements. Nearly all providers recommended screening, however, only 3 patients were directly asked about screening preferences. Few patients were asked about prostate cancer knowledge (2), urological symptoms (3), or family history (6). Most providers discussed disadvantages (80%) and advantages (80%) of PSA screening. Average OPTION score was 25/100 (range 0-67) per provider. Our study found limited SDM during PSA screening consultations. The counseling that did take place utilized components of SDM but inconsistently and incompletely. We must improve SDM for PSA screening for diverse patient populations to promote health equity. This study highlights the need to improve SDM for PSA screening.
PMID: 38822923
ISSN: 1557-1920
CID: 5662852

Barriers to Implementing Registered Nurse-Driven Clinical Decision Support for Antibiotic Stewardship: Retrospective Case Study

Stevens, Elizabeth R; Xu, Lynn; Kwon, JaeEun; Tasneem, Sumaiya; Henning, Natalie; Feldthouse, Dawn; Kim, Eun Ji; Hess, Rachel; Dauber-Decker, Katherine L; Smith, Paul D; Halm, Wendy; Gautam-Goyal, Pranisha; Feldstein, David A; Mann, Devin M
BACKGROUND:Up to 50% of antibiotic prescriptions for upper respiratory infections (URIs) are inappropriate. Clinical decision support (CDS) systems to mitigate unnecessary antibiotic prescriptions have been implemented into electronic health records, but their use by providers has been limited. OBJECTIVE:As a delegation protocol, we adapted a validated electronic health record-integrated clinical prediction rule (iCPR) CDS-based intervention for registered nurses (RNs), consisting of triage to identify patients with low-acuity URI followed by CDS-guided RN visits. It was implemented in February 2022 as a randomized controlled stepped-wedge trial in 43 primary and urgent care practices within 4 academic health systems in New York, Wisconsin, and Utah. While issues were pragmatically addressed as they arose, a systematic assessment of the barriers to implementation is needed to better understand and address these barriers. METHODS:We performed a retrospective case study, collecting quantitative and qualitative data regarding clinical workflows and triage-template use from expert interviews, study surveys, routine check-ins with practice personnel, and chart reviews over the first year of implementation of the iCPR intervention. Guided by the updated CFIR (Consolidated Framework for Implementation Research), we characterized the initial barriers to implementing a URI iCPR intervention for RNs in ambulatory care. CFIR constructs were coded as missing, neutral, weak, or strong implementation factors. RESULTS:Barriers were identified within all implementation domains. The strongest barriers were found in the outer setting, with those factors trickling down to impact the inner setting. Local conditions driven by COVID-19 served as one of the strongest barriers, impacting attitudes among practice staff and ultimately contributing to a work infrastructure characterized by staff changes, RN shortages and turnover, and competing responsibilities. Policies and laws regarding scope of practice of RNs varied by state and institutional application of those laws, with some allowing more clinical autonomy for RNs. This necessitated different study procedures at each study site to meet practice requirements, increasing innovation complexity. Similarly, institutional policies led to varying levels of compatibility with existing triage, rooming, and documentation workflows. These workflow conflicts were compounded by limited available resources, as well as an implementation climate of optional participation, few participation incentives, and thus low relative priority compared to other clinical duties. CONCLUSIONS:Both between and within health care systems, significant variability existed in workflows for patient intake and triage. Even in a relatively straightforward clinical workflow, workflow and cultural differences appreciably impacted intervention adoption. Takeaways from this study can be applied to other RN delegation protocol implementations of new and innovative CDS tools within existing workflows to support integration and improve uptake. When implementing a system-wide clinical care intervention, considerations must be made for variability in culture and workflows at the state, health system, practice, and individual levels. TRIAL REGISTRATION/ NCT04255303;
PMID: 38781006
ISSN: 2561-326x
CID: 5654912

Mixed methods assessment of the influence of demographics on medical advice of ChatGPT

Andreadis, Katerina; Newman, Devon R; Twan, Chelsea; Shunk, Amelia; Mann, Devin M; Stevens, Elizabeth R
OBJECTIVES/OBJECTIVE:To evaluate demographic biases in diagnostic accuracy and health advice between generative artificial intelligence (AI) (ChatGPT GPT-4) and traditional symptom checkers like WebMD. MATERIALS AND METHODS/METHODS:Combination symptom and demographic vignettes were developed for 27 most common symptom complaints. Standardized prompts, written from a patient perspective, with varying demographic permutations of age, sex, and race/ethnicity were entered into ChatGPT (GPT-4) between July and August 2023. In total, 3 runs of 540 ChatGPT prompts were compared to the corresponding WebMD Symptom Checker output using a mixed-methods approach. In addition to diagnostic correctness, the associated text generated by ChatGPT was analyzed for readability (using Flesch-Kincaid Grade Level) and qualitative aspects like disclaimers and demographic tailoring. RESULTS:ChatGPT matched WebMD in 91% of diagnoses, with a 24% top diagnosis match rate. Diagnostic accuracy was not significantly different across demographic groups, including age, race/ethnicity, and sex. ChatGPT's urgent care recommendations and demographic tailoring were presented significantly more to 75-year-olds versus 25-year-olds (P < .01) but were not statistically different among race/ethnicity and sex groups. The GPT text was suitable for college students, with no significant demographic variability. DISCUSSION/CONCLUSIONS:The use of non-health-tailored generative AI, like ChatGPT, for simple symptom-checking functions provides comparable diagnostic accuracy to commercially available symptom checkers and does not demonstrate significant demographic bias in this setting. The text accompanying differential diagnoses, however, suggests demographic tailoring that could potentially introduce bias. CONCLUSION/CONCLUSIONS:These results highlight the need for continued rigorous evaluation of AI-driven medical platforms, focusing on demographic biases to ensure equitable care.
PMID: 38679900
ISSN: 1527-974x
CID: 5651762

Trial Participants' Perceptions of the Impact of Ecological Momentary Assessment on Smoking Behaviors: Qualitative Analysis

Stevens, Elizabeth R; Li, Rina; Xiang, Grace; Wisniewski, Rachel; Rojas, Sidney; O'Connor, Katherine; Wilker, Olivia; Vojjala, Mahathi; El-Shahawy, Omar; Sherman, Scott E
BACKGROUND/UNASSIGNED:Ecological momentary assessment (EMA) is an increasingly used tool for data collection in behavioral research, including smoking cessation studies. As previous addiction research suggests, EMA has the potential to elicit cue reactivity by triggering craving and increasing behavioral awareness. However, there has been limited evaluation of its potential influence on behavior. OBJECTIVE/UNASSIGNED:By examining the perspectives of research participants enrolled in a tobacco treatment intervention trial, this qualitative analysis aims to understand the potential impact that EMA use may have had on smoking behaviors that may not have otherwise been captured through other study measures. METHODS/UNASSIGNED:We performed a qualitative analysis of in-depth interviews with participants enrolled in a pilot randomized controlled trial of a tobacco treatment intervention that used SMS text messaging to collect EMA data on smoking behaviors. In the pilot randomized controlled trial, combustible cigarette and e-cigarette use and smoking-related cravings were measured as part of an EMA protocol, in which SMS text messaging served as a smoking diary. SMS text messaging was intended for data collection only and not designed to serve as part of the intervention. After a baseline assessment, participants were asked to record daily nicotine use for 12 weeks by responding to text message prompts that they received 4 times per day. Participants were prompted to share their experiences with the EMA text messaging component of the trial but were not directly asked about the influence of EMA on their behaviors. Transcripts were coded according to the principles of the framework for applied research. The codes were then examined, summarized, and grouped into themes based on the principles of grounded theory. RESULTS/UNASSIGNED:Interviews were analyzed for 26 participants. The themes developed from the analysis suggested the potential for EMA, in the form of an SMS text messaging smoking diary, to influence participants' smoking behaviors. The perceived impacts of EMA text messaging on smoking behaviors were polarized; some participants emphasized the positive impacts of text messages on their efforts to reduce smoking, while others stressed the ways that text messaging negatively impacted their smoking reduction efforts. These contrasting experiences were captured by themes reflecting the positive impacts on smoking behaviors, including increased awareness of smoking behaviors and a sense of accountability, and the negative impacts on emotions and smoking behaviors, including provoking a sense of guilt and triggering smoking behaviors. CONCLUSIONS/UNASSIGNED:The collection of EMA smoking behavior data via SMS text messaging may influence the behaviors and perceptions of participants in tobacco treatment interventions. More research is needed to determine the magnitude of impact and mechanisms, to account for the potential effects of EMA. A broader discussion of the unintended effects introduced by EMA use is warranted among the research community.
PMID: 38270520
ISSN: 2291-5222
CID: 5625222

Longitudinal association between e-cigarette use and respiratory symptoms among US adults: Findings from the Population Assessment of Tobacco and Health Study Waves 4-5

Karey, Emma; Xu, Shu; He, Pan; Niaura, Raymond S; Cleland, Charles M; Stevens, Elizabeth R; Sherman, Scott E; El-Shahawy, Omar; Cantrell, Jennifer; Jiang, Nan
BACKGROUND:We assessed longitudinal effects of e-cigarette use on respiratory symptoms in a nationally representative sample of US adults by combustible tobacco smoking status. METHODS:We analyzed Waves 4-5 public-use data from the Population Assessment of Tobacco and Health Study. Study sample included adult respondents who reported no diagnosis of respiratory diseases at Wave 4, and completed Waves 4-5 surveys with no missing data on analytic variables (N = 15,291). Outcome was a validated index of functionally important respiratory symptoms based on 7 wheezing/cough questions (range 0-9). An index score of ≥2 was defined as having important respiratory symptoms. Weighted lagged logistic regression models were performed to examine the association between e-cigarette use status at Wave 4 (former/current vs. never use) and important respiratory symptoms at Wave 5 by combustible tobacco smoking status (i.e., never/former/current smokers), adjusting for Wave 4 respiratory symptom index, sociodemographic characteristics, secondhand smoke exposure, body mass index, and chronic disease. RESULTS:Among current combustible tobacco smokers, e-cigarette use was associated with increased odds of reporting important respiratory symptoms (former e-cigarette use: adjusted odds ratio [AOR] = 1.39, 95% confidence interval [CI]: 1.07-1.81; current e-cigarette use: AOR = 1.55, 95% CI: 1.17-2.06). Among former combustible tobacco smokers, former e-cigarette use (AOR = 1.51, 95% CI: 1.06-2.15)-but not current e-cigarette use (AOR = 1.59, 95% CI: 0.91-2.78)-was associated with increased odds of important respiratory symptoms. Among never combustible tobacco smokers, no significant association was detected between e-cigarette use and important respiratory symptoms (former e-cigarette use: AOR = 1.62, 95% CI: 0.76-3.46; current e-cigarette use: AOR = 0.82, 95% CI: 0.27-2.56). CONCLUSIONS:The association between e-cigarette use and respiratory symptoms varied by combustible tobacco smoking status. Current combustible tobacco smokers who use e-cigarettes have an elevated risk of respiratory impairments.
PMID: 38421978
ISSN: 1932-6203
CID: 5644112

Identifying meta-research with researchers as study subjects: Protocol for a scoping review

Laynor, Gregory; Stevens, Elizabeth R
BACKGROUND:Meta-research in which researchers are the study subjects can illuminate how to better support researchers and enhance the development of research capacity. Comprehensively compiling the literature in this area can help define best practices for research capacity development and reveal gaps in the literature. However, there are challenges to assessing and synthesizing the breadth of the meta-research literature produced. METHODS:In this article, we discuss the current barriers to conducting literature reviews on meta-research and strategies to address these barriers. We then outline proposed methods for conducting a scoping review on meta-research with researchers as study subjects. DISCUSSION/CONCLUSIONS:Due to its interdisciplinary nature, broad scope, and difficult to pinpoint terminology, little is known about the state of meta-research with researchers as the study subjects. For this reason, there is a need for a scoping review that will identify research performed in which researchers were the study subjects.
PMID: 38768101
ISSN: 1932-6203
CID: 5654202

Reducing prescribing of antibiotics for acute respiratory infections using a frontline nurse-led EHR-Integrated clinical decision support tool: protocol for a stepped wedge randomized control trial

Stevens, Elizabeth R; Agbakoba, Ruth; Mann, Devin M; Hess, Rachel; Richardson, Safiya I; McGinn, Thomas; Smith, Paul D; Halm, Wendy; Mundt, Marlon P; Dauber-Decker, Katherine L; Jones, Simon A; Feldthouse, Dawn M; Kim, Eun Ji; Feldstein, David A
BACKGROUND:Overprescribing of antibiotics for acute respiratory infections (ARIs) remains a major issue in outpatient settings. Use of clinical prediction rules (CPRs) can reduce inappropriate antibiotic prescribing but they remain underutilized by physicians and advanced practice providers. A registered nurse (RN)-led model of an electronic health record-integrated CPR (iCPR) for low-acuity ARIs may be an effective alternative to address the barriers to a physician-driven model. METHODS:Following qualitative usability testing, we will conduct a stepped-wedge practice-level cluster randomized controlled trial (RCT) examining the effect of iCPR-guided RN care for low acuity patients with ARI. The primary hypothesis to be tested is: Implementation of RN-led iCPR tools will reduce antibiotic prescribing across diverse primary care settings. Specifically, this study aims to: (1) determine the impact of iCPRs on rapid strep test and chest x-ray ordering and antibiotic prescribing rates when used by RNs; (2) examine resource use patterns and cost-effectiveness of RN visits across diverse clinical settings; (3) determine the impact of iCPR-guided care on patient satisfaction; and (4) ascertain the effect of the intervention on RN and physician burnout. DISCUSSION:This study represents an innovative approach to using an iCPR model led by RNs and specifically designed to address inappropriate antibiotic prescribing. This study has the potential to provide guidance on the effectiveness of delegating care of low-acuity patients with ARIs to RNs to increase use of iCPRs and reduce antibiotic overprescribing for ARIs in outpatient settings. TRIAL Identifier: NCT04255303, Registered February 5 2020, .
PMID: 37964232
ISSN: 1472-6947
CID: 5631732

Considerations for using predictive models that include race as an input variable: The case study of lung cancer screening

Stevens, Elizabeth R; Caverly, Tanner; Butler, Jorie M; Kukhareva, Polina; Richardson, Safiya; Mann, Devin M; Kawamoto, Kensaku
Indiscriminate use of predictive models incorporating race can reinforce biases present in source data and lead to an exacerbation of health disparities. In some countries, such as the United States, there is therefore a push to remove race from prediction models; however, there are still many prediction models that use race as an input. Biomedical informaticists who are given the responsibility of using these predictive models in healthcare environments are likely to be faced with questions like how to deal with race covariates in these models. Thus, there is a need for a pragmatic framework to help model users think through how to include race in their chosen model so as to avoid inadvertently exacerbating disparities. In this paper, we use the case study of lung cancer screening to propose a simple framework to guide how model users can approach the use (or non-use) of race inputs in the predictive models they are tasked with leveraging in electronic health records and clinical workflows.
PMID: 37844677
ISSN: 1532-0480
CID: 5609662

Recognizing the value of meta-research and making it easier to find

Stevens, Elizabeth R; Laynor, Gregory
Meta-research is a bourgeoning field studying topics with significant relevance to health sciences librarianship, such as research reproducibility, peer review, and open access. As a discipline that studies research itself and the practices of researchers, meta-research spans disciplines and encompasses a broad spectrum of topics and methods. The breadth of meta-research presents a significant challenge for identifying published meta-research studies. Introducing a subject heading for meta-research in the controlled vocabularies of literature databases has the potential to increase the visibility of meta-research, further advance the field, and expand its impact on research practices. Given the relatively recent designation of meta-research as a field and its expanding use as a term, now is the time to develop appropriate indexing vocabulary. We seek to call attention to the value of meta-research for health sciences librarianship, describe the challenges of identifying meta-research literature with currently available key terms, and highlight the need to establish controlled vocabulary specific to meta-research.
PMID: 37928126
ISSN: 1558-9439
CID: 5635132