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Background Music therapy (MT) programs have been used in various health care settings to reduce patients’ pain, anxiety, and stress. However, few studies have investigated its effects on patients with spinal cord injury (SCI), a frequently serious event requiring extensive rehabilitation. Objective This pilot study evaluated the feasibility of offering music-assisted relaxation (MAR) during rehabilitation for patients with SCI. We also measured the effect of MAR on the patients’ pain, anxiety, and stress levels. Methods Patients were hospitalized at Mayo Clinic (Rochester, Minnesota) from September 2015 through September 2017 for rehabilitation of an SCI. Eligible patients received 2, 20-minute, personalized MAR sessions. Interventions were facilitated by a board-certified music therapist (MT-BC) and included diaphragmatic breathing, guided imagery, and passive muscle relaxation with live guitar accompaniment and spoken, improvised, or singing voice. Two surveys (Generalized Anxiety Disorder [GAD-7] and Perceived Stress Scale [PSS-10]) were used at the time of study consent and again upon hospital dismissal. Pain, anxiety, and relaxation were assessed before and after both MT sessions with visual analog scales (VASs), scored from 0 to 10. Participants completed a 7-question satisfaction survey after the second MAR session. Results Twenty patients were enrolled (12 men, 8 women); 13 (65%) completed the MAR interventions. The mean (SD) age was 53.7 (17.7) years. VAS scores for pain significantly improved after both sessions (P ≤ .02). VAS scores for anxiety also significantly improved after both sessions (P ≤ .02), as did VAS scores for relaxation (P ≤ .02 for both). The satisfaction survey indicated that patients generally believed that they benefited from MT. Rehabilitation staff indicated that MT did not interfere with routine clinical care. Conclusion MT with live MAR is a feasible treatment for patients with SCI and may be effective for reducing their pain and anxiety.

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) is the process of administering intravenous (IV) antimicrobials outside the acute inpatient setting. Oral antimicrobials for complex infections are referred to as complex outpatient antimicrobial therapy (COpAT). OPAT/COpAT programs are expanding, as are the opportunities for clinical Infectious Diseases (ID) pharmacists (RPHs) involvement. The current state of clinical (non-dispensing) role and the functions being performed by RPHs in OPAT/COpAT is unknown. Methods To define the current state of OPAT/COpAT pharmacy practice across the United States (US), specifically the clinical functions performed by RPHs, design of RPH involved OPAT/COpAT clinics, and compare training of RPHs who practice in OPAT/COpAT to ID RPHs who do not, a survey of a possible 31 questions was emailed to the American College of Clinical Pharmacists (ACCP) Infectious Diseases Practice and Research Network (PRN) email list. Results were focused on US-based respondents. Results Eighty-seven RPHs responded with 27 practicing in OPAT/COpAT. Training background did not differ between groups. Programs with an OPAT/COpAT RPH were more likely to have a formal OPAT team compared to those without an OPAT/COpAT RPH (p < 0.001). OPAT/COpAT RPHs were early in their careers, with roughly half practicing < 5 years in ID, and 66.7% practicing < 5 years in OPAT/COpAT. Most OPAT/COpAT RPHs (66.7%) practiced at an academic medical center with a median full time equivalent (FTE) of 1 RPH. Most (63%) utilized a collaborative practice agreement and 81.5% shared job functions with other ID RPH roles, most commonly antimicrobial stewardship. Few (28%) OPAT/COpAT programs involved a dispensing component. The average daily census was 42 patients followed by an OPAT/COpAT RPH. There was wide variability in the types of tasks ID RPH performed in OPAT/COpAT, the three most important tasks are listed in Figure 1. OPAT Pharmacists Task Ranking by Importance There was wide variability in the types of tasks ID pharmacist performed in OPAT/COpAT. The most OPAT/COpAT pharmacists responded that adjusting medications based on lab values was in their top 3 most important clinical tasks. When ranking the top three most important tasks, selecting the initial OPAT/COpAT regimen was ranked first most often, followed by review of review of OPAT appropriateness for discharge, then adjusting medications based on lab values. Conclusion This is the largest known survey of OPAT/COpAT RPHs. RPH involvement in OPAT/COpAT in the US is an emerging trend with wide variability in program structure. Tasks performed by OPAT/COpAT RPHs varied significantly; however, OPAT/COpAT RPH respondents’ functions are largely clinical in nature. Disclosures All Authors: No reported disclosures

Abstract Background Lyme disease, the most common tickborne disease in the United States, may be prevented by taking a single 200-mg dose of oral doxycycline after a high-risk bite from a blacklegged tick. Currently, it is not known how Lyme disease post-exposure prophylaxis (PEP) might vary by region and healthcare system. We identified single-dose doxycycline medication orders in three healthcare systems in states with high incidence of Lyme disease and compared associated patient and provider characteristics. Methods Electronic health record data during 2012 – 2016 were obtained from three healthcare systems: Geisinger (Pennsylvania), Marshfield Clinic (Wisconsin), and Mayo Clinic (Minnesota/Wisconsin). Creation of analytic variables and analysis were harmonized across the three sites. Medication orders for single-dose doxycycline ≤200 mg that were accompanied by specific key words or diagnostic codes (e.g., tick bite; Lyme disease prevention) were considered evidence of PEP. Manual chart review was performed from a random subset to evaluate the algorithms used to identify PEP. Results Among 2,937,585 patients with at least one medication order or clinical encounter during the study period, 14,102 single-dose doxycycline orders for Lyme disease PEP for 13,172 unique patients were identified. The typical patient receiving PEP was older (mean age 51 – 58 years), male (56 – 59%), and non-Hispanic White (81 – 98%). The annual seasonality of medication orders was bimodal, with peaks occurring during April – July and October – November. The most common encounter setting was an outpatient clinic or urgent care center (80 – 91%); medication orders after patient phone calls in the absence of an in-person visit occurred frequently (14 – 19%) in two health systems. Chart abstractions (n=600) revealed instances of PEP prescribed inappropriately (e.g., bite from a non-blacklegged tick; patient with symptoms of acute Lyme disease). Conclusion Lyme disease PEP with a single dose of doxycycline was frequently prescribed in healthcare systems where there is a high incidence of Lyme disease. PEP was most commonly prescribed to non-Hispanic Whites over the age of 50 years. Public health initiatives for tickborne disease prevention should include clinician education on the appropriate use of Lyme disease PEP. Disclosures Anna M. Schotthoefer, PhD, HelixBind (Other Financial or Material Support, salary support) John Zeuli, PharmD, INSMED (Other Financial or Material Support, honoraria for educational speaking)

Abstract Background Although trimethoprim-sulfamethoxazole (TMP-SMX) has consistently demonstrated significant interindividual variability, therapeutic drug monitoring is used to optimize dosing and avoid adverse reactions that may contribute to treatment interruption. While data exists on the use of SMX level monitoring in pneumocystis, there is a lack of data in SMX serum monitoring utility for invasive Nocardia infections. Methods We retrospectively reviewed adults who received TMP-SMX to treat nocardial brain abscess (BA) and underwent SMX testing level from January 2010 to December 2020. Results Overall, 24 patients had Nocardia spp. BA; Twenty-two (91.7%) were treated with TMP-SMX, and 16/22 (72.7%) had a documented SMX serum level. The median age was 64 (IQR 58-69) years, and the majority were males (77.3%). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a higher prevalence of hemodialysis (HD, 42.9% vs. 33%; P=.99) and malignancy (50% vs. 33.3%; P=.65). The most common BA location was the frontal lobe (43.8% vs. 33.3%; P=.99), with a single (68.8% vs. 50%; P=.62) and smaller (1.3 vs. 1.9 cm; P=.58) brain fluid collection, and with fewer midline shift (6.3% vs. 16.7%; P=.48), respectively. The median TMP-SMX duration was 350 days (P=.31). The most common dosing was 2-double strength, three times a day (31.8%). The SMX median level was 158.5 (IQR 120-218) mcg/mL, collected at two hours (75%) post-administration in the induction phase (81.3%). The most common recommendation was to continue therapy based on the level results. Eleven (46%) patients had a level >150 mcg/mL, and 5 (45.5%) reported drug toxicity, including nausea in 3, acute kidney injury in 2, and thrombocytopenia in 2 patients. Ninety-four percent of the patients with SMX levels had surgical intervention for therapeutic purposes vs. 83% of those without it (P=.65). A total of 11 (50%) patients were cured, 3 (18.8%) relapsed, and 2 (12.5%) died. Conclusion Patients with SMX serum level monitoring are more likely to be on HD, during the induction phase and among those with higher and more frequent dosing. About half of patients with SMX levels >150 mcg/mL experienced drug toxicity; however, SMX levels did not impact patient outcome and length of treatment. Disclosures All Authors: No reported disclosures

Background: Patients who undergo cardiac surgery are at increased risk of stroke, postoperative cognitive decline, and delirium. These neurocognitive complications have led to increased costs, intensive care unit stays, morbidity, and mortality. As a result, there is a significant push to mitigate any neurological complications in cardiac surgery patients. Near-infrared spectroscopy to measure regional cerebral oxygen saturations has gained consideration due to its non-invasive, user-friendly, and relatively inexpensive nature. Aim of Study: To provide a comprehensive summary of cerebral oximetry in cardiac surgery. The review interrogates multiple systematic reviews assessing different outcomes in cardiac surgery to assess if cerebral oximetry is effective. Further, the review analyzes all available interventions for an acute desaturation to determine the efficacy of individual interventions. Methods: A narrative review of randomized controlled trials, observational studies, and systematic reviews with metanalyses were performed through August 2021. Results: There is significant heterogeneity amongst studies regarding the definition of a clinically significant cerebral desaturation. In addition, the assessment of neurocognitive outcomes has large variability, making metanalysis challenging. To date, cerebral oximetry use during cardiac surgery has not been associated with improvements in neurocognitive outcomes, morbidity, or mortality. The evidence to support particular interventions for an acute desaturation is equivocal. Conclusions: Future research is needed to quantify a clinically significant cerebral desaturation and to determine which interventions for an acute desaturation effectively improve clinical outcomes.

Abstract Background: Central nervous system (CNS) lymphoma, both primary and secondary disease, carries the worst prognosis of all Non-Hodgkin’s lymphoma with a 5 year survival of less than 30% with current therapeutic options. Recent studies have shown constitutive activation of both NF-κB and MAPK signaling pathways in the maintenance and progression of CNS lymphoma. This often coincides with mutations in MYD88. IRAK4 is a serine/threonine kinase that mediates interleukin 1 receptor (IL-1R) and Toll-like receptor (TLR) signaling downstream of MYD88, and is a novel therapeutic target for this disease. CA-4948 is an oral first-in-class small molecule inhibitor of IRAK4 that has demonstrated clinical activity in patients with systemic Non-Hodgkin’s Lymphoma. Our study goal was to evaluate CA-4948 efficacy in a syngeneic preclinical model of primary CNS B cell lymphoma (A20), supporting future clinical investigation of this agent in this difficult to treat disease. Materials and Methods: Plasma, cerebrospinal fluid (CSF), and brain tissue (both naïve and tumor bearing) were assessed for CA-4948 drug concentration following single high-dose oral administration using UPLC-MS/MS. Biomarker expression, including NF-κB and MAPK, was measured in control and CA-4948 treated brain tissue resected from tumor-bearing animals using multi-parameter immunohistochemistry and 3D modeling of cleared tissue. Dose-dependent survival responses were also measured using the A20 preclinical model of primary CNS lymphoma. Results: While brain concentrations of CA-4948 remained low with respect to plasma (~4-5%), therapeutic dose levels were attained in both CSF and brain tissue (>502 nM). No significant difference between naïve and A20 tumor bearing brain tissue was observed, indicating the blood brain barrier remained intact in this model. Biomarker analyses revealed significant downregulation of both MAPK and NF-κB signaling pathways in response to CA-4948, as evidenced by reduced protein levels of phospho-p38Thr180/Tyr182, phospho-ERK1/2Thr202/Tyr204, and phospho-p65Ser536 in both the tumor cells and the tumor microenvironment. Finally, CA-4948 treatment produced a dose-dependent survival response in syngeneic animals harboring CNS A20 tumors. Conclusions: CA-4948 is able to reach therapeutic dose levels in the CNS in a preclinical murine model of CNS lymphoma, producing significant and dose-dependent anti-tumor activity and survival advantage. These data support further evaluation of CA-4948 in clinical investigation and treatment of patients with CNS lymphoma. Citation Format: Christina A. von Roemeling, Bently P. Doonan, Lan Hoang-Minh, Han W. Tun, Elizabeth Martinez, Raul Soikes, Reinhard von Roemeling, Duane A. Mitchell. The IRAK4 inhibitor CA-4948 demonstrates antitumor activity in a preclinical model of CNS lymphoma [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P243.

Abstract With the development of various strategies of anti-CD19 immunotherapy for treatment of B cell malignancies, it remains to be elucidated whether CD19 targeting with a monoclonal antibody impairs subsequent CD19 targeted chimeric antigen receptor T cell (CART19) therapy. In this study, we evaluated the potential interference between the CD19 targeting monoclonal antibody tafasitamab and CART19 treatment (using a construct similar to the FDA approved therapy, FMC63-41BBζ, tisagenlecleucel) in preclinical lymphoma and leukemia models. For in vitro assays, the CD19 + cell lines JeKo-1 (mantle cell lymphoma), Nalm6 (acute lymphoblastic leukemia), and OCI-Ly7 (diffuse large B cell lymphoma) were used. When CART19 were co-cultured with CD19 + tumor cells in the presence of increasing concentrations of tafasitamab (10-400 µg/mL) or the isotype control, an impairment of CART19 functions at the highest concentration of tafasitamab was observed. However, when tafasitamab was cocultured with tumor cells overnight and removed from the culture by washing, there was no impairment of CART19 anti-tumor activity or effector functions compared to a pre-culture with isotype control. We then aimed to validate these findings in xenograft mouse models by determining whether prior tafasitamab treatment impairs subsequent CART cell function. First, a two-step JeKo-1 xenograft model was created through inoculation of 1x10 6 luciferase + JeKo-1 cells to immunocompromised NOD-SCID-γ -/- (NSG) mice via tail vein injection. One week later, tumor burden was assessed by bioluminescence imaging (BLI) and mice were randomized to receive either 1) PBS (Group 1) or 2) 10 mg/kg of tafasitamab (Group 2) (Fig. 1A). Treatment was performed until the mice reached the endpoint due to the high tumor load. When reaching the endpoint, mice were euthanized and spleen was harvested. Splenic cells were then injected to naïve NSG mice. Two weeks after the inoculation of splenic cells (PBS or tafasitamab treated), mice were imaged with BLI and randomized according to their tumor burden to receive 2x10 6 of 1) untransduced T cells (UTD) or 2) CART19 (i.v.) (Fig. 1B). Mice, treated with CART19 demonstrated potent anti-tumor effects and showed prolonged survival compared to UTD control mice. Interestingly, CART19-treated mice inoculated with Group 2 splenic cells (pretreated with tafasitamab) showed a significantly better tumor control and overall survival compared with mice engrafted Group 1 splenic cells (PBS pretreatment) (Fig. 1C). This finding led us to further investigate the effects of prior tafasitamab therapy on subsequent CART19 treatment. In this context, we studied the sequential treatment with tafasitamab and CART19 in an additional JeKo-1 xenograft model (Fig. 1D). In brief, NSG mice were inoculated with luciferase + JeKo-1 on day -14. On day -8, mice were imaged and randomized to the PBS (Group I) or tafasitamab (10 mg/kg) group. On day -1 tafasitamab treated mice were imaged again, randomized to the tafasitamab discontinuation (Group II) or continuation (Group III). Treatment with PBS was continued in Group I. All groups were administered with 1x10 6 of CART19 on day 0. Cotreatment of JeKo-1 xenografts with tafasitamab and CART19 led to impaired anti-tumor activity presumably as a result of CD19 binding competition between tafasitamab and CART19 (Group III). Mice treated with tafasitamab followed by CART19 had improved tumor control compared to mice treated with PBS followed by CART19 (Fig. 1E-F). Serial peripheral blood analysis demonstrated that mice from Group I showed the highest CART19 expansion on day 10. Strikingly, Group II exhibited weak CART19 expansion at day 10, but strongest expansion on day 23 (Fig. 1G). We therefore hypothesized that prior treatment with tafasitamab results in modulation of CART19 cell activation. To test this hypothesis, spleens of satellite mice were harvested 24 hours after CART19 administration. Flow cytometric analysis revealed that the mice from Group II showed significantly lower CD69 and HLA-DR expression on CART19 cells compared with Group I, and reduced apoptosis as measured by the Annexin assay (Fig. 1H-I). In summary, concomitant treatment of tafasitamab and CART19 led to impaired anti-tumor activity while, in contrast, sequential treatment of tafasitamab and CART19 did not inhibit CART19 anti-tumor activity but rather promoted anti-tumor effects in xenograft models. Figure 1 Figure 1. Disclosures Sakemura: Humanigen: Patents & Royalties. Augsberger: MorphoSys AG: Current Employment. Schanzer: MorphoSys AG: Current Employment. Patra-Kneuer: MorphoSys AG: Current Employment. Heitmüller: MorphoSys AG: Current Employment. Steidl: MorphoSys AG: Current Employment. Endell: MorphoSys AG: Current Employment. Ding: DTRM: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees. Parikh: Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Bristol Myers Squibb, Merck, AbbVie, and Ascentage Pharma: Research Funding; Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie: Membership on an entity's Board of Directors or advisory committees. Kay: Acerta Pharma: Research Funding; Targeted Oncology: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Research Funding; Behring: Membership on an entity's Board of Directors or advisory committees; CytomX Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tolero Pharmaceuticals: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Agios Pharm: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Sunesis: Research Funding. Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cox: Humanigen: Patents & Royalties. Kenderian: Humanigen, Inc.: Consultancy, Honoraria, Research Funding.

Abstract Background: Palliative care (PC) benefits patients with cancer and those undergoing hematopoietic stem cell transplantation (HSCT), but remains under-utilized in HSCT. While transplant physicians have substantial concerns regarding how patients perceive PC, studies examining HSCT recipients' perceptions of PC are lacking. Methods: Between 11/2020-4/2021, the CIBMTR Survey Research Group conducted a multi-site cross-sectional survey of adult autologous and allogeneic HSCT recipients at 11 transplant centers in the United States who were 3-12 months post-transplant to assess their experience, knowledge, and perceptions of PC. Using validated questionnaires, we assessed patients' familiarity with PC, knowledge and perception of PC, unmet PC needs, quality of life, and symptom burden. We computed a composite score of patients' perceptions of PC (mean = 48.8, SD = 12.2). We used a generalized linear regression model to examine factors associated with patients' perceptions of PC. Results: Of 359 potentially eligible patients, 250 (69.6%) enrolled in the study and 249 were eligible for analysis. Median participant age was 58.1 years (IQR 16.6). Most were white (85.9%), non-Hispanic or Latino (95.2%), and male (53.0%). Overall, 63.1% underwent autologous HSCT. The most common diagnoses were multiple myeloma (42.2%), lymphoma (22.1%), leukemia (16.9%), and MDS/MPN (12.4%). Overall, 44.2% (110/249) of patients reported limited knowledge about PC and 51.0% (127/249) endorsed being familiar with PC. Most patients stated that when they hear the term PC, they feel hopeful (54%), and reassured (50%) while a minority reported feeling scared (21%), stressed (22%), or depressed (15%) [Figure 1]. Most endorsed that when a PC referral is suggested for them, they think their doctor really cares about what is happening to them (83%), and only 7% of patients stated that when a PC referral is suggested, they think their doctor has given up on them [Figure 2]. In multivariate analyses, patients who were more knowledgeable about PC were more likely to have a positive perception of PC (B = 7.54, SE=1.61, P < 0.001) compared to those who had less knowledge about PC. Patients with postgraduate education were more likely to have a negative perception of PC (B = -5.55, SE=2.60, P = 0.034) compared to those with high school education or less. Patients' demographics, HSCT type, diagnosis, unmet PC needs, quality of life, and symptom burden were not statistically significantly associated with their perceptions of PC. Conclusions: A substantial proportion of HSCT recipients report limited knowledge and familiarity with PC. Most patients reported positive perceptions of PC, and those who were more knowledgeable about PC were more likely to have positive perceptions of PC. These data do not support transplant physicians' concerns about how patients perceive PC and underscore the need for future interventions to further educate patients about PC to overcome barriers to PC utilization in HSCT. Figure 1 Figure 1. Disclosures Burns: Astellas Pharma Inc.: Research Funding; Medac GmbH: Research Funding; Sanofi: Research Funding; OncoImmune: Research Funding; Fate: Research Funding; Bristol Meyers Squibb: Research Funding; PrioThera: Research Funding; Kyowa Kirin International: Research Funding. Murthy: CRISPR Therapeutics: Research Funding. LeBlanc: Amgen: Consultancy, Other: travel; Pfizer: Consultancy, Other: Advisory Board; AstraZeneca: Consultancy, Honoraria, Other: Advisory board, Research Funding; Flatiron: Consultancy, Other: Advisory board; Agios: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Other: Travel fees, Research Funding, Speakers Bureau; Daiichi-Sankyo: Consultancy, Honoraria, Other: Advisory board; AbbVie: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; Helsinn: Consultancy, Research Funding; Duke University: Research Funding; Jazz Pharmaceuticals: Research Funding; UpToDate: Patents & Royalties; NINR/NIH: Research Funding; CareVive: Consultancy, Other, Research Funding; Otsuka: Consultancy, Honoraria, Other; American Cancer Society: Research Funding; Seattle Genetics: Consultancy, Other: Advisory board, Research Funding; Astellas: Consultancy, Honoraria, Other: Advisory board; Heron: Consultancy, Honoraria, Other: advisory board.