2024 ICTS Symposium Poster Abstracts

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Early Stage

Poster #	Poster Details
1	King, Skylar PhD University of Missouri – Columbia Surfactant Protein A Promotes Atherosclerosis through Mediating Macrophage Foam Cell Formation King SD, Cai D, Pillay AS, Fraunfelder MF, Allen LH, Chen SY Introduction: Atherosclerosis (AT) is a progressive cardiovascular disease characterized by persistent inflammation and excessive cholesterol deposition within the artery wall and is the fundamental pathological process underlying coronary artery disease and stroke. Macrophage (MФ) foam cells play a central role in the pathogenesis of AT. Surfactant protein A (SPA) is a lipid-associating protein involved with regulating macrophage function in various inflammatory diseases. However, the role of SPA in atherosclerosis and macrophage foam cell formation has not been investigated. Given that AT is associated with dyslipidemia and inflammation, we hypothesized that SPA functions to enhance MФ foam cell formation resulting in increased AT. Methods: Primary resident peritoneal macrophages were extracted from wild-type (WT) and SPA deficient (SPA-/-) mice to determine the functional effects of SPA in macrophage foam cell formation. SPA expression was assessed after pro-atherosclerotic stimuli in macrophages, in healthy vessels and atherosclerotic aortic tissue from the human coronary artery and WT or apolipoprotein e-deficient (ApoE-/-) mice brachiocephalic arteries fed high-fat diets (HFD) for 4 weeks. Hypercholesteremic WT and SPA-/- mice fed an HFD for 6 weeks were investigated for atherosclerotic lesions in vivo. Results: In vitro experiments revealed that global SPA deficiency reduced intracellular cholesterol accumulation and macrophage foam cell formation. Mechanistically, SPA-/- dramatically decreased cluster of differentiation antigen 36 (CD36) cellular and mRNA expression. SPA expression was increased in atherosclerotic lesions in humans and ApoE-/- mice. In vivo SPA deficiency attenuated atherosclerosis and reduced the number of lesion-associated macrophage foam cells. Impact: Our results elucidate that SPA is a novel factor for atherosclerosis development. SPA enhances macrophage foam cell formation and atherosclerosis through increasing scavenger receptor CD36 expression and thus, increasing OxLDL uptake. These findings suggest that the modulation of SPA could be a novel approach for reducing AT.
2	Lagas, Joseph MA Washington University in St. Louis Improving CRISPR/Cas9 Editing Efficiency to Generate a GBA1 KO due to Pseudogene-induced Homology Directed Repair Lagas JS, Sentmanat MF, Wang ZT, Cui X Introduction: The capability to translate research to the clinic is contingent upon the ability to study disease-causing mutations from patients in a cell type specific manner. This is most commonly accomplished through the introduction of these disease-causing mutations in induced pluripotent stem cells (iPSCs) and their subsequent differentiation. However, in certain cases, editing these genes can be complicated by the existing DNA repair mechanisms in human cells. The GESC received a request to induce a knock-out of the human beta-glucocerebrosidase gene (GBA), a gene with mutations commonly associated with Parkinson’s disease and Gaucher disease, in an iPSC line with CRISPR/Cas9. Methods: gRNA-Cas9 RNP specifically targeting the gene was introduced by nucleofection and editing was analyzed in the pool via next generation sequencing of the targeted amplicon. Results: While a high percentage of insertions or deletions (indels) was expected, we instead observed most alignments in the pool had no indels present. Instead, the majority of alignments displayed single base pair mismatches (SNPs) at the gRNA target and downstream of the site. These SNPs match mismatches that are commonly seen in a GBA pseudogene (GBAP) which is 16kb downstream of GBA. These genes frequently undergo homology directed repair (HDR) in human cells making the identification of new disease-causing mutations and the introduction of these mutations difficult. To outcompete the pseudogene for HDR at the target site, we designed two single stranded donor DNA sequences (ssODNs) containing 7 bp and 10 bp deletions and introduced them via nucleofections along with the RNP. The introduction of the ssODNs improved indel percentage of the pool by ~10% bringing the total percentage of indels in the pool above 25%. Impact: This study provides a novel method to improve the introduction and study of disease-causing mutations in the GBA gene to human cells.
3	Maeng, Ju Heon PhD Washington University in St. Louis Epigenetic Therapy Activates TE-chimeric Transcripts to Provide an Additional Source of Glioblastoma HLA-I Antigens Maeng JH, Jang HJ, Shah NM, Liang Y, Basri NL, Ge J, Qu X, Mahlokozera T, Tzeng S, Williams RB, Moore MJ, Annamalai D, Chen JY, Lee H, DeSouza PA, Li D, Xing X, Kim AH, Wang T Introduction: Inhibiting epigenetic modulators can transcriptionally reactivate transposable elements (TEs). These TE transcripts often generate unique peptides that can serve as novel antigens for immunotherapy. Here, we asked if TEs activated by epigenetic therapy could appreciably increase the antigen repertoire in glioblastoma, an aggressive brain cancer with low mutation and neoantigen burden. Methods: We treated patient-derived primary glioblastoma stem cell lines, and an astrocyte and fibroblast primary cell line with epigenetic therapy, and identified treatment-induced, TE-derived transcripts that are preferentially expressed in cancer cells. Results: We verified that these transcripts could produce HLA-I-presented antigens using LC-MS/MS pulldown experiments. Importantly, many TEs were also transcribed, even in proliferating non-tumor cell lines, after epigenetic therapy, which suggests that targeted strategies like CRISPRa could minimize potential side-effects of activating unwanted genomic regions. Impact: This work presents a cautionary, yet promising, tale for future translational efforts in harnessing treatment-induced TE-derived antigens for targeted immunotherapy.
4	Mahjoubnia, Alireza MSc University of Missouri – Columbia Digital Light 4D Printing of Bioresorbable Shape Memory Elastomers for Personalized Aneurysm Occlusion Mahjoubnia A, Cai D, Wu Y, King SD, Torkian P, Chen AC, Talaie R, Chen S, Lin J Introduction: Globally, aneurysms affect 2-5% and afflict millions in the U.S., presenting significant health threats due to their high rupture rate that can lead to death. Conventional aneurysm coil treatments grapple with problems such as adverse bodily reactions, biocompatibility issues, and a recurrence risk of about 20%, with complete occlusion failures in 10-15% of patients because of geometrical incompatibility. Although 4D-printing technology creates new prospects for creating custom biomedical implants, finding suitable materials remains an ongoing challenge. Methods: Utilizing digital light 4D-printing, a shape memory elastomer (SME) was engineered by synthesizing glycerol dodecanoate acrylate prepolymer (pre-PGDA) with an acrylic acid monomer to establish a crosslinked Poly(glycerol dodecanoate acrylate)-Polyacrylic acid (PGDA-PAA) structure. This development included biocompatibility testing and vascular grafting experiments. A personalized coil was then crafted and applied to a 3D-printed aneurysm flow model derived from a real patient. Results: At a precision of ~150 microns, the 4D-printed SME can recover its shape when exposed to body temperatures, thereby imitating the mechanical properties of soft tissues. Tests showed that the material supported over 90% cell growth and improved cell adherence. In vivo vascular grafting experiments demonstrated regeneration of the aorta after implantation. This versatility, combined with the material’s capacity for absorption, suggests it could potentially be replaced by natural tissue. Endovascularly deployment of 4D-printed coils within a flow model endorses this minimally invasive technique. The inclusion of tantalum in the coils significantly improves their radiopacity, which aids in the exact positioning and tracking of the coils after insertion, thus enhancing the effectiveness of the procedure. Impact: This advance in 4D-printing highlights the PGDA-PAA elastomer’s biocompatibility, biodegradability, mechanical properties, making it an excellent choice for implantation. Fabricating patient-specific embolization coils represents a proof of concept that 4D printed coils flawlessly deploy in situ, reducing complications after surgery.
5	Pinni, Sai BS Washington University in St. Louis Evaluating the Effect of an Ovine Acellular Dermal Matrix on Breast Implant Capsule Formation Using a Rodent Model Pinni SL, Fadell N, Martin C, Marsh E, Wood MD, Sacks JM Introduction: Implant-based breast augmentation is one of the most common cosmetic surgeries with over one million procedures performed to date using silicone implants. In 2022, 78% of breast reconstruction surgeries after mastectomy were also implant-based. Despite this popularity, over 10% of patients experience postoperative capsular contracture, potentially resulting in pain and distorted appearance. Current literature suggests wrapping implants in acellular dermal matrices (ADM) may reduce capsule formation. In partnership with the medical technology company TELA Bio, we investigated the inflammatory response to lab-made silicone breast implants with and without TELA Bio’s ovine ADM in a rodent surgical model. Methods: Ten female Lewis rats each had two lab-made hemispherical silicone implants inserted bilaterally into the prepectoral space. The left implant was wrapped in ADM using TELA Bio’s OviTex® PRS Reinforced Tissue Matrix. Implant pockets were irrigated with antibiotic solution before and after insertion. Implants were harvested en bloc at a 12-week endpoint for tissue histology and immunohistochemistry. Outcome measures included capsular thickness and immune cell infiltration. Results: Preliminary histological analysis showed no significant difference in average capsule thickness between the non-ADM implants (102±43 µm, n=7) and ADM-wrapped implants (128±43 µm, n=8) (p=0.256). Further analysis will include immune cell infiltration of the capsules (i.e., monocytes and macrophages, M2 pro-regenerative phenotype), as well as all outcomes at two additional deeper tissue sections. Impact: Our study showcases successful partnership with industry to investigate a solution to a postoperative complication of one of plastic surgery’s most common procedures. Leveraging our lab’s expertise in animal models and ability to create rodent-sized silicone breast implants, our anatomically-relevant model allows for better understanding of how acellular dermal matrices can affect capsule formation around breast implants. This model also enables future investigation of capsular contracture causes (e.g., biofilms) and other complications like Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).
6	Ribaudo, Joseph BS Washington University in St. Louis Next Generation of Tissue Adhesive for Obliteration of Surgical Dead Space Ribaudo JG, Xia X, Mullen C, Saffari T, Colchado D, Li X, Sacks JM Introduction: Many surgical procedures create large dead spaces prone to fluid accumulation, leading to hematomas and seromas. Drains are used to prevent these complications, but they often cause patient discomfort and have potential for infection. Our objective is to develop a biodegradable tissue adhesive with strong adhesion and biocompatibility to obliterate surgical dead space. Methods: We synthesized a hydrogel-based tissue adhesive with polyester backbone brush polymers featuring carboxyl and N-hydroxysuccinimide ester functional groups. Adhesive strength to rat subcutaneous tissue, fat and fascia was evaluated using a universal testing machine (n=3). We evaluated the heat release of our adhesive when applied to rat rectus abdominus fascia (n=3) using a FLIR camera. Cyanoacrylate was used as control. Cytocompatibility of our adhesive was tested at various concentrations (0, 7, 14, and 21 mg/mL) on human umbilical vein endothelial cells, using LIVE/DEAD staining and the alamarBlue. Lastly, we varied the percentage of double bonds in our adhesive (100%, 40%, and 25%) to test tunable biodegradability. Each was placed in PBS for four weeks and was weighed weekly. Results: The shear tests demonstrated similar strength between our tissue adhesive and cyanoacrylate for subcutaneous tissue to fat (27.9 vs. 26.0 kPa, p=0.58) and subcutaneous tissue to fascia (28.7 vs. 25.0 kPa, p=0.76). Thermal analysis demonstrated that cyanoacrylate led to a peak tissue temperature of 29 ºC, compared to 24.8 ºC for our adhesive. After 24 hours, there was no significant decrease in cell viability at any concentration of our adhesive. Lastly, after four weeks, the 100% double bond adhesive retained nearly its original weight, the 40% double bond adhesive was 60% of its original weight, and the 25% double bond adhesive was 15% of its original weight. Impact: Our novel tissue adhesive has demonstrated strong adhesion, tunable biodegradability, and biocompatibility. It has potential to obliterate dead space from surgical procedures in any area of the body. Its subcutaneous use may provide a comfort and safety advantage for use in many procedures, decreasing drain usage and incidence of seromas and hematomas.

Clinical

Poster #	Poster Details
7	Davis, Trevor MD Washington University in St. Louis Botulinum Toxin Improves Quality of Life and Clinical Outcomes in Pediatric Defecation Disorders Davis TA, Turner A, Wilson C, Wang J, Joerger S, Utterson EC, Shakhsheer BA Introduction: While internal anal sphincter (IAS) Botox has been increasingly utilized in children with disordered defecation (DD), no literature regarding clinical efficacy or quality of life (QoL) influence exists. Therefore, we aimed to elucidate the effect of IAS Botox as an adjunct to standard treatment for DD on patient/caregiver QoL metrics in association with corresponding clinical outcomes. Methods: Consecutive children undergoing IAS Botox for DD prospectively completed surveys at baseline, two-weeks, and three-months post-procedure. Time points included assessment of clinical symptoms (Rome IV Questionnaire), QoL (Pediatric Quality of Life Inventory [PedsQL]), and caregiver well-being/family functioning (PedsQL-Family Impact Module [PedsQL-FIM]). Results: Of 60 participants, median age was 7 years (IQR 4-10) with 34 (56.7%) males and 32 (53.3%) first-time Botox recipients. Median onset of positive effect after Botox was 6 days (IQR 3-14), while median loss of effect was 70 days (IQR 39-83). Compared to baseline, by three months there was a lower chance of meeting Rome IV criteria for functional constipation in first-time recipients (RR 0.73, 95%CI: 0.58-0.91;p=0.005). This remained significant after adjusting for any bowel regimen change during the three-month period following Botox (OR 0.33, 95%CI: 0.13-0.74;p=0.012). Regarding QoL, there was significant improvement in total PedsQL score at both two-weeks (11.79 point improvement, 95%CI: 6.36-17.22;p<0.0001) and three-months (13.97 point improvement, 95%CI: 8.47-19.47;p<0.0001) from baseline for first-time recipients, while improvement was only observed at two-weeks for prior recipients (6.67 point improvement, 95%CI: 0.65-12.69;p=0.030). First-time recipients demonstrated significant improvements in total PedsQL-FIM score at both two-weeks (9.33 point improvement, 95%CI: 3.77-14.89;p=0.001) and three-months (11.57 point improvement, 95%CI: 5.94-17.20;p<0.0001) from baseline. Impact: Our findings establish far-reaching benefits of IAS Botox, both clinically and psychosocially, suggesting that appropriate incorporation into the treatment paradigm may globally enhance outcomes in children with DD.
8	Galati, Bridget DO Washington University in St. Louis COVID-19 Vaccination Rates and Hesitancy Among Postpartum Individuals with Substance Use Disorders Galati BM, McGuire S, Wenzinger ML, Rogers CE, Kelly JC Introduction: Pregnant individuals with substance use disorders (SUD) are at higher risk of developing severe complications from COVID-19. Infants < 6 months are also at significant risk. Vaccination in perinatal individuals can help protect both mother and infant from severe outcomes; however, vaccine hesitancy is high. We evaluated COVID-19 vaccination rates among postpartum patients with SUD and identified reasons for vaccine hesitancy. Methods: Conducted a telephone survey and retrospective chart review in a SUD-specific wraparound perinatal clinic. Results: Retrospective chart review included 207 postpartum patients. 80.7% were prescribed medication for SUD. 34.3% had received ≥ 1 COVID-19 vaccination, with 45.1% receiving 1, 47.9% receiving 2, and 7.0% completing 3. Vaccination rates within the past 5 years for Tdap and influenza were higher (65.7%, p=<0.00001 and 42.5%, p=0.105508). COVID-19 vaccination rate was significantly higher than the rate within another non-SUD high-risk outpatient obstetric clinic at our institution (n=130), which had a rate of 12.0% (p =<0.00001). 20 postpartum patients completed the survey, of which 65.0% were < 6 months postpartum. 40.0% received at least one COVID-19 vaccination, most having received vaccination before/during pregnancy (81.8%). Top reason to vaccinate was to protect themselves and their child(ren) (81.8%), followed by provider recommendation (45.5%) and friends/family encouraged vaccination (45.5%). Top reasons not to included concern about side effects (66.7%), potential fetal risks (55.6%), and unvaccinated household (44.4%). Barriers to vaccination - inaccessible, inconvenient, no provider recommendation, medical condition or allergy, lack of trust in vaccines or providers -- were very rarely reported (0.0-11.1%). 20.0% strongly/agreed that individuals with SUD are more likely to be hospitalized/die from COVID-19. 40.0% reported plans to vaccinate their infant, of which 50.0% were vaccinated themselves. Top infant vaccine hesitancy reasons included concern about side effects and limited long-term vaccination data (83.3%). Impact: Wraparound clinics for obstetric individuals with SUD may help provide preventive healthcare beyond SUD treatment.
9	McPherson, Laura DPT, PhD Washington University in St. Louis Pathophysiology of Voluntary Motor Commands in People with Multiple Sclerosis Identified Using Reverse Engineering of Motor Unit Population Discharge McPherson LM, Reece TM, Simon S, Lohse K, Negro F, Lang C, Naismith R, Cross AH Introduction: Multiple sclerosis (MS) causes central nervous system lesions that alter neural communication between the brain and the spinal motoneurons that activate muscles. These voluntary motor commands consist of three components that must be appropriately balanced for skilled motor control: excitation, inhibition, and neuromodulation. Disruption of this balance has harmful effects, evidenced by work in spinal cord injury, stroke, and aging. In MS, we have no knowledge about voluntary motor commands or how they relate to common motor deficits (weakness, spasms, gait difficulty). The heterogeneity of MS across patients makes systematic research of neurophysiological correlates of motor deficits difficult. Here, we use a novel paradigm for reverse engineering of motor unit population discharge to characterize excitatory, inhibitory, and neuromodulatory components of the voluntary motor command in MS on a person-specific basis. Methods: We tested 24 MS patients with a variety of motor deficits and disability levels. Eight reverse engineering variables were calculated from motor unit spike trains decomposed from high-density surface EMG of the tibialis anterior and soleus during plantarflexion and dorsiflexion. Results: Three variables reflecting the pattern of inhibition were significantly lower in MS than controls, indicating inhibition that scales proportionally with excitation and contributes to weakness in hemiparetic stroke. The MS group was significantly more variable, with values higher and lower than controls. Some abnormalities were seen in patients without disability, indicating our measures may be sensitive to subclinical changes in voluntary motor commands. Impact: Little is known about neural mechanisms underlying motor impairments in MS, limiting the development of targeted neuroplasticity-inducing therapies that are emerging in other neurological populations. Our study identifies how voluntary motor commands are pathological in MS on a group basis and provides insight into their variability. Future work will examine whether there are subgroups in the MS population whose different voluntary motor command pathologies could be targeted with novel neurorehabilitation interventions.
10	Pickett, Carley DO Saint Louis University Cardiovascular Medications and Overall Survival in Metastatic Hormone-sensitive Prostate Cancer Pickett CR, Ingram K, Eaton Jr DB, Tohmasi S, Karunanandaa K, Gopukumar D, Puri V, Schoen MW Introduction: Assessment of comorbid cardiovascular disease can predict health outcomes and may risk-stratify patients for adverse events and death. Current methods used to estimate patient risk, such as the Charlson Comorbidity Index (CCI), are based on International Classification of Diseases (ICD) codes, which are a poor indicator of severity and complexity of comorbid disease. In this study, we examined the relationship between cardiovascular medications and survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Methods: In a nationwide retrospective observational study of US Veterans with de novo mHSPC in the VA Health Administration between 2011-2021, we determined the number of cardiovascular drugs prescribed in the year prior up to 14 days before initiation of treatment. Multivariable logistic regression and Cox proportional hazard modeling was used to assess the association between number of drugs with overall survival and mortality. Results: Among 7,875 veterans, a median of 2 (1-4) unique cardiovascular medications were filled in the year prior to treatment. The mean age was 74 years (SD 10.0) with a median CCI of 3 (3-6). Age was associated with increased number of cardiac medicines (p<0.001). Increased number of medications was associated with decreased OS using the Kaplan-Meier method (p<0.001). The overall survival was 28 months for veterans on 2 medications (aHR 1.15, CI 1.06-1.26), 27 months on 3 medications (aHR 1.15, CI 1.06-1.26), 25 months on 4 medications (aHR 1.18, CI 1.07-1.30), and 23 months on 5+ medications (aHR 1.27, CI 1.15-1.41). After adjusting for age, race, BMI, weight change, PSA, and CCI, the number of medications was independently associated with increased mortality, (aHR 1.05, CI 1.03-1.06) for each additional cardiac medication. Impact: The number of cardiovascular medications is associated with decreased overall survival and increased mortality in veterans undergoing treatment for mCRPC. Our findings suggest that clinicians can use cardiovascular medications as a simple, reliable tool to estimate comorbid disease and potentially guide treatment discussions in patients with prostate cancer.
11	Sanchez, Justin BA Washington University in St. Louis Optimizing the Work of Learning for Burnout Prevention: A Randomized Pilot Study of an Online CBT-based Intervention in Medical Students Sanchez JS, Perry D, Martin V, Gray T, Nicol GE Introduction: Burnout in medical trainees significantly increases their risk of suicidal ideation, and trainees are often reluctant to seek mental health care. Digital mindfulness and cognitive behavioral therapy (CBT) principles are evidence-based preventative strategies for reducing burnout and increasing professional satisfaction. We are conducting a randomized pilot study to assess whether digital interventions for CBT-based training are a feasible way to improve wellbeing and reduce burnout in medical students. Methods: We are comparing a CBT-based online intervention (OptimalWork) that employs cognitive restructuring, mindfulness, and behavioral activation, with a podcast-listening (control) intervention to promote wellbeing in medical students. Wellbeing is measured via the Human Flourishing Index (HFI,max=100) and the OptimalWork Inventory (OWI,max=240), which assesses idealism, work-engagement, work-life-harmony, and friendships. Higher scores indicate better adaptive functioning. Additionally, Likert-scale-based assessments of stress, anxiety, depression, emotional support, and burnout are being collected at baseline, 4, 8, 12, and 16 weeks. Results: Enrollment began September 2023. To date, 35 WUSM students (70% female, 27\|18\|33\|22% M1\|M2\|M3\|Other) have been randomized. At baseline, mean HFI was 67(s.d.=13), indicating a relatively high degree of overall flourishing. Mean OWI was 131(24), with only 19%(n=6) and 22%(n=7) endorsing high work engagement and work-life harmony, respectively; 81%(n=26) and 61%(n=19) endorsed high idealism and supportive relationships, respectively. 46%(n=15) reported high (“fairly” or “very often”) stress and 25%(n=8) high work-exhaustion. 78%(n=25) reported high emotional support, 13%(n=4) anxiety, and 7%(n=2) depression. Longitudinal data collection to evaluate intervention effectiveness and relationships between student characteristics, educational context and wellbeing is ongoing. Impact: These preliminary results demonstrate the feasibility and accessibility of fully-remote digital mental health interventions and suggest that work engagement and work-life-harmony may represent opportunities for health promotion and burnout prevention in medical students.

Health Services/Population Health

Poster #	Poster Details
12	Anidi, Nwaliweaku BPT Washington University in St. Louis Moving Towards Consensus in the Responsible Conduct of Dissemination and Implementation Research: A Scoping Review Anidi NF, Aboagye-Mensah G, Doering M, Antes A, Powell BJ, Huffman MD, Tetteh EK Introduction: Dissemination and implementation (D&I) research, crucial in translating evidence into practice, is yet to be included as a separate study design category for ethical consideration. Researchers are asking relevant questions about how current ethical standards can be applied to D&I trials. The responsible conduct of D&I research requires an adaptation of existing bioethical frameworks that reflect D&I’s unique study designs, intervention targets, and corresponding risks. We aim to conduct a scoping review to explore the availability, breadth, and consistency of published literature on the responsible conduct of dissemination and implementation research to generate an evidence synthesis report. Methods: We searched PubMed, Web of Science, and Google Scholar from February 2006 to July 2023 for relevant literature and managed them with Covidence. The search used a combination of standardized terms and keywords including bioethics, ethics, research standards, responsible research, health services research and implementation. Results: We have screened 794 article abstracts and are currently conducting 153 full-text reviews. Some emerging themes from our findings include barriers and challenges to the ethical integration of interventions to health settings, and ethical frameworks for specific domains of D&I research. The literature also includes important discussions about ethical board reviews of quality improvement studies and the ethics of implementing health systems interventions in LMICs. Upon completion of the literature review, we will conduct a concept mapping of all the emerging themes. Impact: Our work has the potential to affect Policy TSBM benefits, by generating scientific research reports and developing consensus standards. Moreover, we argue that the community and public health benefits of implementing interventions through a D&I tailored ethical lens, cannot be understated. Our project is the first step in a roadmap to develop a framework using a Delphi approach for assessing the responsible conduct of D&I research.
13	Bello Kottenstette, Jennifer MD, MSCP Saint Louis University Contraceptive Uptake in Postpartum People with Opioid Use Disorder and Opioid Use with Co-Occurring Substance Use Bello Kottenstette J, Xu K, Salas J, Kelly J, Grucza R Introduction: Delaying pregnancy allows people with opioid use disorder (OUD) to choose when they are ready to continue their families. We aim to address the lack of characterization of postpartum contraceptive uptake among people with OUD compared to people without OUD. Methods: Analyses used 73,811 pregnancy episodes among 61,221 people (2016-2021) from the St. Louis University-SSM Virtual Data Warehouse. OUD was defined from the year prior and through pregnancy. Contraceptive uptake was defined within 90-days after delivery. We used generalized estimating equations to assess the association of OUD +/- co-occurring substance use disorders (SUDs) with any contraception (yes/no) and type of contraception (effective – pills, patch, vaginal ring, injection, or highly effective – long-acting reversible, LARC methods (intrauterine device, implant) and sterilization). Results: The sample was 66.0% white and average age was 27.7 years (±5.6). About one-third of pregnancies were followed by contraception initiation, 2.3% had an associated OUD diagnosis, and 1.3% OUD with co-occurring SUD. There was no association between OUD and 90-day postpartum contraception receipt, but OUD was associated with decreased receipt of postpartum LARC methods and sterilization compared to user-dependent methods such as oral contraception (aOR=0.76; 95% CI: [0.64-0.91]). Having a co-occurring SUD in addition to OUD was associated with decreased postpartum contraception uptake across all contraception types (aOR=0.81[0.70-0.93]) and highly-effective methods specifically (aOR=0.48[0.38-0.61]). Impact: Overall contraception uptake among people with OUD is comparable to uptake in the non-OUD population. Those having co-occurring SUDs in addition to OUD are particularly unlikely to receive contraception. The reasons people choose contraceptive methods are complex, and not solely based on method effectiveness and may differ based on severity of substance use disorder. More information is needed to understand the complex factors that impact decision making around postpartum contraception initiation that maintains patient autonomy and reduces stigma.
14	Chen, Justin MD, MHPE Washington University in St. Louis Stakeholder Perspectives of a HFrEF Polypill: A Multi-center Mixed Methods Study Chen JC, DeJong C, Agarwal M, Hairston AM, Durstenfeld MS, McKay V, Huffman MD, Hsue PY, Agarwal A Introduction: A polypill containing all four classes of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection (HFrEF) has been proposed to change the heart failure treatment paradigm. The acceptability, appropriateness, and feasibility of a HFrEF polypill-based strategy is unknown. The purpose of this study was to elicit patients’ and providers’ priorities in the design of HFrEF polypills in the U.S. Methods: From April 2023 to December 2023, we conducted a convergent mixed-methods study at Washington University in St. Louis (WUSTL), University of California, San Francisco (UCSF), and the American College of Cardiology (ACC). We administered physician surveys using adapted implementation outcome measures and conducted in-depth interviews with patients, cardiologists, general internists, and advanced practice providers. We conducted thematic qualitative analysis guided by the Consolidated Framework for Implementation Research v2.0. Results: Out of 224 survey respondents across the United States, participants agreed that HFrEF polypills are highly acceptable (mean [SD], 4.2 [0.7]), highly appropriate (4.1 [0.8]), and highly feasible (4.1 [0.7]). Key themes emerged from interviews with patients and providers including 1) medication adherence, variations in clinical practice, and access to healthcare are determinants of HFrEF care, 2) variations in HFrEF polypill design may influence uptake, 3) equitable implementation of HFrEF polypills will be influenced by cost, and 4) future research priorities including evaluation of effectiveness and implementation. Impact: A HFrEF polypill-based strategy was acceptable, appropriate, and feasible by patients and physicians. Participants described key priorities, including HFrEF polypill components, titratability, and effects on health equity, that will inform the design and implementation of future trials.
15	Kuan, Yuan-Hung BS Washington University in St. Louis Prediction of In-hospital Mortality Using Artificial Intelligence to Handle Incomplete and Time-varying Intensive Care Unit Data Kuan YH, Wang M, Li JS, Chang SH Introduction: Accurate prediction of Intensive Care Unit (ICU) patients’ mortality is crucial for healthcare professionals to make informed decisions, ultimately improving patient outcomes. However, ICU data are collected irregularly at different time points; therefore, these data are oftentimes incomplete and heterogeneous, hindering the performance of model-based statistical methods. This study aimed to use artificial intelligence (AI) to develop a machine learning (ML) model to predict in-hospital mortality among ICU patients. Methods: We retrieved 8,000 adult patients admitted to ICU from the MIMIC II Clinical Database, a public use database provided in PhysioNet/CinC Challenge 2012. For each patient, 11 time-varying clinical variables (including vital signs and laboratory results) were collected irregularly during the first 48 hours after ICU admission. These patients were divided into training (50%) and testing (50%) sets. We then excluded patients with <5 available data points. We first used previously developed ML method to impute data for each variable by filling in a value at every 15-minute time interval. Patients in the training set were used to develop an ML model using deep neural network (DNN) to classify patients based on in-hospital mortality. The model performance was tested in the testing set using 3 metrics: (1) true positive rate (TPR): % of deaths being correctly identified, (2) positive predicted value (PPV): % of model identified deaths being actual deaths; and (3) accuracy: % of correct predictions. Results: A total of 3,599 patients (515 in-hospital deaths) with 11 time-varying clinical variables were included in the training set. Each variable contained 192 time points after imputation. In the testing set of 3,618 patients (541 in-hospital deaths), the developed model achieved a TPR of 0.90, a PPV of 0,85, and accuracy of 0.78 for predicting in-hospital mortality. Impact: We successfully used AI techniques to develop a model for predicting in-hospital mortality based on irregular time-varying ICU data. Our study demonstrates the potential of AI to prescreen high-risk patients at ICU for intervention to prevent in-hospital mortality and to assist clinical decision making.
16	La Manna, Anna MSW, MPH Washington University in St. Louis Translating for Impact: A Free Online Toolkit for Demonstrating the Larger Impact of Your Work La Manna AM, LaBrier M, Andersen S, Heidbreder J, Combs T, Brossart L, Luke D Introduction: In an increasingly competitive budgetary environment, we must be able to demonstrate the health and societal benefits of clinical and translational research. The Translational Science Benefits Model (TSBM) is a framework for evaluating the downstream health and social impact of research. The TSBM team created the online Translating for Impact Toolkit to help researchers at any stage plan, track, and demonstrate their work’s impact in four domains: clinical, community, economic, and policy. Methods: Development of the online toolkit included 6 phases: 1) Review of existing tools, 2) Development of fillable tool prototypes, 3) Pilot testing, 4) Development of online tools, 5) Usability testing, and 6) Refinement of online tools. First, we reviewed existing tools for measuring research impact. We then created prototypes of nine tools, published on the TSBM website, and pilot tested with researchers. Based on feedback, we developed and launched online Translating for Impact Toolkit. Next, we will conduct usability testing with researchers to evaluate ease-of-use and quality, identify areas for improvement, and refine and publish the final toolkit. Results: Researchers can create user accounts, add projects, invite collaborators, and save progress as they complete the nine tools in the Translating for Impact Toolkit. The tools are divided into three steps: Plan (Roadmap to Impact, Benefits 2×2, Partner Mapper, and Team Manager), Track (Impact Tracker), and Demonstrate (Product Navigator, Case Study Builder, Impact Profile, and Dissemination Planner). A toolkit dashboard provides a quick snapshot of translational impact for each project. The toolkit will help both individual scientists and Clinical and Translational Science Award (CTSA) hubs evaluate the impact of their work. Impact: The TSBM online toolkit is a free, secure, easy-to-use platform researchers can use to plan, track, and demonstrate the impact of their work. The toolkit provides a structured process that will help the next generation of scientists prioritize and promote translational impact in their work. To date, more than 250 researchers have created user accounts and begun using the toolkit.
17	LaBrier, Mia MPH Washington University in St. Louis Translating for Equity Impact: A Community-engaged Approach to Integrate Health Equity into the Translational Science Benefits Model LaBrier M, La Manna A, Andersen S, Brossart L, Combs T, Heidbreder J, Casey S, Luke D Introduction: There have been increased efforts to recognize the effects, or lack thereof, of scientific research on health equity. The Translational Science Benefits Model (TSBM) is a framework for evaluating the impact of research on health and society. The TSBM team is currently integrating equity into the TSBM framework. Methods: Adaptation of the TSBM involved 3 phases: 1) Literature review; 2) Community engagement sessions; and 3) Model refinement. First, we conducted a review of the clinical and translational sciences literature addressing at least one of the 30 TSBM benefits in relation to health equity. Next, we held two engagement sessions, one in St. Louis, MO, and one in Madison, WI, with community members including leaders in local community-based organizations, in order to incorporate professional expertise and lived experience in the model adaptation. We will use their input to prioritize and refine adaptations to the model. Results: Our literature review identified equity dimensions of the original 30 TSBM benefits and 15 potential additional benefits for inclusion in the model, including community partnerships, community capacity building, workforce development, and social determinants of health. The community engagement sessions provided key insights for adapting the model and determining the most important equity benefits to evaluate. In the Madison session, members highlighted the importance of broader equity in relation to health, like access to transportation. Community organization leaders in the St. Louis session emphasized the need to build and prioritize relationships throughout the research process. The TSBM team is currently making final adaptations, which will provide an expanded approach to evaluating the impact of scientific activities to include impacts on health equity. Impact: The TSBM provides a framework for clinical and translational scientists to plan for, track, and demonstrate the broader impacts of their work. Including equity impacts in the model can help increase consideration of equity in science and more clearly make the link between research and equity impact.
18	Lukas, Stephanie PharmD, MPH University of Health Sciences and Pharmacy Medication Saving Behaviors and Hoarding: Subgroup Analyses of Correlations in Black and Non-black Families Lukas SK, Schmidtke KA, Washington TN, VanDyke MM Introduction: Medication hoarding describes a persistent difficulty of discarding or parting with medications that are no longer useful. This behavior can result in mis-dosing and inappropriate sharing, leading to adverse consequences (Sorenson, 2005). Previous research has found correlations between medication savings behavior, hoarding, and medication adherence (Warren et al., 2019; VanDyke et al., 2018), but these studies did not include subgroup analyses. In this study, we explore whether the patterns obtained from previous research extend to two racial subgroups. Methods: We conducted a retrospective cross-sectional study using the same dataset as the aforementioned research. The dataset consisted of 119 dyads, comprising a female caregiver taking care of older family members. Participants were split into two groups including Black (n=30) and non-Black (n=89). For each group, correlations were examined between scores from the Adherence to Refills and Medications Scale, Hoarding Rating Scale and Savings Inventory Revised Composite, and Medication Saving Behavior questionnaire. Regression analyses were then used to compare these relationships across the groups. Results: For both groups, significant correlations were found between adherence and medication savings behavior (rs >0.42) and between medication savings behavior and hoarding (rs >0.34). However, significant correlations between adherence and hoarding only appeared for those who did not identify as Black (r=0.59) but not for those who identified as Black (r=0.15). Although this difference is not significant, these results may not be reliable. We need 337 participants to find a correlation of 0.15 significant with an alpha of 0.05 and a beta of 0.20, but our sample of Black participants was only 30. Impact: By analyzing existing data, policies can be formed to assist affected families. The present findings suggest that needs may differ across races. However, they do not reveal what services could be developed or how they could be delivered, so we recommend conducting mixed-method or qualitative research to understand how or in what ways to help families struggling with medication hoarding.
19	Markee, Michael PhD, DPT Saint Louis University Differences in Physical Therapy Utilization by Surgical Setting after Lower Extremity Joint Replacement Markee MD, Ravipathi P, Chrusciel T Introduction: Patients receiving a lower extremity joint replacement (LEJR) are commonly prescribed physical therapy (PT) to address pain, range of motion, and function. As LEJRs are more commonly performed in an outpatient setting, particularly in a younger population, patients are less likely to receive inpatient PT, potentially resulting in increased utilization of community-based (home health and outpatient) PT. The purpose of this research is to compare the utilization of acute inpatient and community-based PT in patients receiving an inpatient LEJR versus those receiving an outpatient LEJR. Methods: This retrospective cohort study utilized the Optum de-identified electronic health record database from 2010-2018. The cohort included 33,027 patients over 35 years of age who had an LEJR between 2010-2018. The primary outcome of interest was receipt of PT in the 90 days following LEJR in various settings. Covariates included the LEJR setting, race, age, sex, insurance status, geographic region, and Charlson Comorbidity Index. Logistic regression analyses were used to determine the likelihood of PT receipt, and negative binomial regression analyses estimated the amount of PT used. A secondary analysis compared patients < 65 and ≥ 65 years of age. Results: 20,591 patients received PT within 90 days of the LEJR procedure. 16,133 of these were inpatient surgeries and 1,378 were outpatient surgeries. The average days of PT was 7.4 (+/-6.7 days). Adjusted models show those with an inpatient procedure received four times as many days of acute inpatient PT (Rate Ratio 4.01; 95% CI: 3.76-4.27) and 39% more days of community-based PT (RR 1.39; 95% CI: 1.25-1.55) than those with an outpatient procedure. When stratifying by age, the odds of receiving community-based PT was greater in those with an inpatient procedure <65 years of age (OR 1.48; 95% CI 1.32-1.66) but less likely in those > 65 years (OR 0.81; 95% CI 0.73-0.91). Impact: With the rate of LEJR outpatient procedures increasing, attention must be paid to the amount of post-operative PT. Since community-based PT is correlated to improved outcomes, insurers and policymakers should ensure quality and adequate care in community-based PT settings is delivered.
20	McLaughlin, Laura PhD, RN Saint Louis University A Systematic Review of Genomic Education for Nurses and Nursing Students: Sufficient to Prepare the Oncology Nursing Workforce? McLaughlin L, Mahon S, Khemthong U Introduction: The completion of the Human Genome Project in 2003, a monumental scientific achievement that provided the first sequence of the human genome, marked a significant milestone in healthcare. This project laid the foundation for precision medicine, a healthcare approach that considers an individual’s genetic makeup and lifestyle factors in their treatment plans. As precision medicine becomes increasingly prevalent in healthcare, it is crucial for nurses, and other healthcare professionals, to have a solid understanding of fundamental genomic concepts. However, the integration of genomic content into nursing curricula and continuing education is currently limited. This systematic review aims to identify educational strategies for effectively delivering genomics content to nurses. Methods: CINAHL Plus, ERIC, Ovid MEDLINE, and Scopus electronic databases were searched from January 1, 2003, through July 6, 2023. Educational outcomes were categorized using the three domains of learning: cognitive, affective, and psychomotor. A narrative approach synthesized the data using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Results: Ten studies met the inclusion criteria. Quality assessment for bias was conducted independently; study quality ranged from fair to poor. No study used a complete psychometrically tested instrument to measure genomic cognitive or affective knowledge; none measured the psychomotor domain. Impact: The development of effective strategies to deliver genomic education is a pressing need. Equally important is the creation of reliable and valid assessment instruments that can accurately measure the impact of educational interventions, including the psychomotor skills necessary for safe and effective practice.
21	Schmidtke, Kelly Ann PhD University of Health Sciences and Pharmacy A Cluster-Randomized Evaluation of an Intervention to Increase the Use of Statistical Process Control Charts for Hospitals in England Schmidtke KA, Kudrna K, Quinn L, Bird P, Hemming K, Venable Z, Lilford R Introduction: Conversations between hospital board members, middle managers, and frontline staff often revolve around performance metrics, e.g., wait times and hospital-acquired infection rates. Where presentations focus on two-point comparisons (before/after) or targets (e.g., visualized with Red-Amber-Green (RAG) codes), initiatives could chase statistical noise rather than sound statistical signals of poor or superior performance. Statistical process control (SPC) charts make this distinction clear. A training intervention was created to improve the uptake of the SPC charts by hospitals in England. The current study evaluates the effectiveness of that training against the background of a prolonged national initiative to encourage the adoption of SPC charts. Methods: A parallel cluster randomized trial was conducted with hospitals in England that had not yet adopted the SPC methodology. Half were randomized to the training intervention and half to the control. Our primary analysis compares the difference in SPC chart use in hospital board papers between groups in a post-randomization period (adjusting for baseline). Trainees also completed feedback forms. Results: 15 hospitals of similar sizes and deprivation statuses completed the study. SPC chart use increased in both groups (29 and 30 percentage points respectively). Thus, there was no statistically significant difference between the intervention and control hospitals in their use of SPC charts in the post-randomization period (average absolute difference 1% (95% CI:-39 to 42). In the feedback forms, 93.9% (N=31/33) of trainees affirmed learning and 97.0% (N=32/33) had formed an intention to change their behavior. Impact: Control chart use increased in both intervention and control hospitals. While this was not the anticipated finding, it is encouraging. The finding is consistent with a rising tide and/or contamination effect, such that the culture of control chart use is spreading across hospitals in England. Further research is needed to determine the characteristics of the training or culture that facilitated uptake to inform future quality and safety initiatives nationally and internationally.
22	Shih, Yi-Hsuan MS Washington University in St. Louis Quantify Racial Differences in Life Expectancies and Life Years Lost for Populations with MGUS and Multiple Myeloma using Discrete Event Simulation Models Shih YH, Ji M, Huber J, Wang M, Colditz GA, Chang SH Introduction: Multiple myeloma (MM) is an incurable hematological cancer, preceded by an asymptomatic pre-malignant condition – monoclonal gammopathy of undetermined significance (MGUS). Racial disparities have been demonstrated in every stage of MM, with non-Hispanic black (NHB) populations experiencing worse outcomes compared to their non-Hispanic white (NHW) counterparts. To understand and quantify racial disparities, we constructed a discrete-event simulation model to study the natural history of MM in NHB and NHW men and women. Methods: We used data from Centers for Disease Control and Prevention, National Health and Nutrition Examination Survey, Surveillance, Epidemiology, and End Results (SEER), and Veterans Health Administration (VHA) to estimate probabilities of disease-related events: MGUS, MM, and death as well as the distributions of the time to events. The models were further calibrated and validated using the SEER data. For each population, we performed microsimulation and computed age-specific incidence of MGUS/MM, life expectancy (LE), and life years lost (LYL) associated with MGUS/MM, defined as LE without MGUS/MM minus LE with MGUS/MM. Results: For men, LE at the incidence of MGUS/MM was 11.5/6.0 years for the NHB population, compared to 13.2/7.0 years for their NHW counterparts, resulting in LYL of 4.8/9.8 years for the NHB population, compared to 5.0/11.1 years for their NHW counterparts. For women, LE at MGUS/MM was 11.5/6.2 years for the NHB population, compared to 11.8/6.7 years for their NHW counterparts, resulting in LYL of 4.6/8.9 years for the NHB population, compared to 4.8/9.1 years for their NHW counterparts. Impact: The findings from this study provide valuable insights into the interplay between sex, race, and disease outcomes, and thus have the potential to set the goals for MM prevention and control strategies aimed at improving disease outcomes and reducing MM health disparities. Therefore, the findings have profound implication for promoting health equity, deterring disease progression, and improving outcomes among populations inflicted by MGUS and MM.
23	Strober, William MD Washington University in St. Louis Tracheostomy Incidence and Complications: A National Database Analysis Strober WA, Kallogjeri D, Piccirillo JF, Rohlfing ML Introduction: Tracheostomy is a common procedure that is associated with various complications ranging from minor hemorrhages to catastrophic events. An estimated 85,000 tracheostomies were performed per year between 2002-2017 in the United States, but despite the high frequency of tracheostomy procedures, the last study to investigate risk factors associated with tracheostomy complications was performed on a 2006 database. In this study we aimed to describe the incidence of tracheostomy-related complications and identify prognostic risk factors by analyzing a large administrative database. Methods: PearlDiver, a private analytics database of insurance claims from Medicare, Medicaid, and commercial insurance companies, was used to identify patients who underwent tracheostomies and associated complications between January 2010 and October 2021 by CPT and ICD-9/ICD-10 codes. Results: A total of 198,143 tracheostomies were identified from PearlDiver, and at least one tracheostomy-related complication occurred within 90 days of the procedure in 22,802 (10.3%) of these cases. The proportion of tracheostomy-related complications was 2.3 times higher in 2019 compared to 2010 (95% CI: 2.18-2.52). The risk of developing tracheostomy-complications was associated with the hospital region (highest in the Midwest as compared to the West [OR=1.32; 95% CI: 1.25-1.39]), provider specialty (highest for otolaryngologists as compared to nonsurgical physicians [OR=2.22; 95% CI: 2.10-2.34]), insurance plan type (lowest for cash payment compared to Medicaid [OR=0.70, 95% CI: 0.50-0.94]), and Elixhauser Comorbidity Index (ECI) (highest in patients with ECI of 7+ compared to 0-1 [OR=2.96; 95% CI: 2.17-3.24]), but was not significantly associated with patient age (OR=0.99; 95% CI: 0.99-0.99), or sex (OR=1.04; 95% CI: 1.01-1.07). Impact: Complications after tracheostomy are common and sicker patients are at higher risk for complications. Identifying factors associated with increased risk for complications could help to improve patient and family counseling, guide quality improvement initiatives, and inform future studies on tracheostomy outcomes.
24	Xu, Kevin MD, MPH Washington University in St. Louis Postpartum Contraception Use Among People with Opioid Use Disorder: A Multi-state Analysis of Administrative Data in the United States Xu K, Bello Kottenstette J, Buss J, Jones HE, Bierut LJ, Stwalley D, Szlyk HS, Martin CE, Kelly JC, Carter EB, Krans EE, Grucza RA Introduction: Offering medication to treat opioid use disorder (MOUD) together with contraception has the potential to help treatment-seeking people achieve healthy interpregnancy intervals. We used multistate administrative claims to compute rates of contraception utilization in postpartum reproductive-age people starting buprenorphine (BUP) or psychosocial treatment without medication (PSY). Methods: In this retrospective cohort study, we analyzed data from the Merative™ MarketScan® Commercial and Multi-State Medicaid Databases (2016-2021) among reproductive-age postpartum women initiating BUP or PSY. The outcome variable was contraception receipt at 90 days postpartum, ascertained via procedure codes and pharmacy files, encompassing highly-effective methods (permanent contraception and long-acting reversible contraception [LARC], obtained as procedures) and effective user-dependent methods (oral contraception pills [OCPs], patches, and rings obtained via pharmacies; depot/injection obtained via office procedures). We used adjusted multivariable Poisson regression models to measure the association of BUP (vs PSY) receipt on contraception utilization after delivery. Results: Our sample consisted of 11,118 postpartum people initiating BUP or PSY. 2,487(22.4%) and 2,953 (26.6%) were prescribed contraception at 90 days postpartum respectively (9.2% LARC, 6.1% permanent contraception, 0.2% patch, 1.1% ring, 3.9% depot, 1.9% oral). Overall, compared to PSY, BUP receipt during pregnancy was associated with modestly increased likelihood of postpartum contraception uptake (aRR=1.17[1.07-1.28]). BUP was associated with increased uptake of effective user-dependent methods obtained as prescriptions (aRR=1.13[1.08-1.18]), with no relationship observed between BUP and highly-effective contraception procedural methods such as LARC and permanent contraception. Impact: BUP receipt during pregnancy, relative to PSY, conferred an increase in user-dependent contraception uptake but was not associated with increases in contraception requiring office procedures. Contraceptive method preferences of women with OUD may differ by type of OUD treatment and should be taken into account by providers.