Abstract Background Long-acting (LA) cabotegravir/rilpivirine (CAB/RPV) may simplify antiretroviral therapy (ART), improve adherence, and reduce pill stigma for people with HIV (PWH). However, real-world implementation is challenged by various barriers. We describe an integrated LA CAB/RPV workflow and the clinical characteristics and outcomes of PWH referred for and initiated on CAB/RPV in a Ryan White HIV/AIDS Program-funded clinic in South Florida (serving more than 1600 PWH). Methods The clinic engaged an interdisciplinary team (MD/APRN, PharmDs, RNs) to develop and maintain an infrastructure required to transition virologically suppressed (HIV RNA < 50 copies/mL) PWH from oral ART to LA CAB/RPV (Figure 1). MD/APRN referred pre-screened and interested PWH to PharmDs for eligibility evaluation, medication counseling, and drug acquisition. RNs administered injections, scheduled and tracked clinic appointments to ensure on-time injections, and ordered appropriate labs. PWH followed up with MD/APRN every 4 months to ensure efficacy and safety. Results Between January 2022 and March 2023, 83 PWH were referred to PharmDs for initiation of LA CAB/RPV and 30 (36%) initiated LA CAB/RPV. Those not initiated on LA CAB/RPV included those who declined to start (e.g., patient concerns over side effects, convenience) (n=23), clinician adherence concerns (n=9), insurance denial (n=7), and baseline resistance (n=7). Payor source for LA CAB/RPV included 40% RWHAP, 36% private, and 24% Medicare/Medicaid. For those initiated on LA CAB/RPV (Table 1), we observed a mean turnaround time of 23 days from PharmD eligibility evaluation to the first injections. Three PWH discontinued LA CAB/RPV: 2 due to side effects and 1 due to pregnancy. Five PWH experienced low-level viremia (HIV RNA < 200 copies/mL) following the switch, all others maintained viral suppression. Conclusion A large number of eligible and interested PWH referred for LA CAB/RPV did not initiate the drug. Those who initiated CAB/RPV tolerated the drug well and maintained viral suppression. Implementation of LA CAB/RPV is enhanced by an interdisciplinary team to provide services, optimize workflows, and maintain infrastructure needed for a successful program. Disclosures All Authors: No reported disclosures

Background: On-target off-tumor toxicities of anti-CD19 CAR T-cell therapy include B-cell aplasia and hypogammaglobulinemia. Long term B-cell aplasia is hypothesized to represent functional CAR T-cell engraftment (Melenhorst, Nature 2022), while peripheral blood B-cell recovery represents the loss of functional CAR-T cells against target over time. Patients with large B-cell lymphoma (LBCL) who are clinical responders have a 50-70% chance of B-cell recovery in the first year, with the remainder experiencing longer term B-cell aplasia (Logue, Haematologica 2021). Here, we sought to identify factors associated with long term B-cell aplasia using a cohort of responding patients who received CAR T-cell therapy for LBCL. Methods:This retrospective cohort study included 57 patients with LBCL treated with CD19-targeted CAR T-cell therapy between June 2016 and August 2020 at Moffitt Cancer Center who exhibited complete or partial response at six months after CAR T-cell infusion. Patients were treated with with axicabtagene ciloleucel (axi-cel; n=50) or tisagenlecleucel (tisa-cel; n=7), either as standard-of-care therapy (n=47) or as part of a previously published clinical trial (n=10; NCT02348216, NCT03391466, NCT03153462). Peripheral blood B-cells were measured by flow cytometry using CD19 expression as part of routine clinical care at baseline and periodically after infusion. Prolonged B-cell aplasia was defined as a CD19+ B cell count comprising less than 1% of peripheral blood mononuclear cells during a minimum of two separate time points beyond 6 months of follow-up. Patients were defined as having B cell recovery if >1% B-cells were observed in peripheral blood at any time after CAR T-cell infusion. Results: At a median follow up of 33 months (95% CI: 28.7, 37.3 months), 29 (51%) patients had persistent B-cell aplasia and 28 (49%) had recovery of peripheral B-cell counts. Median B-cell count at 12 months in the recovery group was 84/µL (IQR 2.5-197) compared to 0/µL (IQR 0-1) in the aplasia group. Patients with long-term B-cell aplasia had lower CD4 T-cell counts prior to CAR T-cell infusion [median 200/µL (IQR 136-278) vs. 330/µL (IQR 224-451); P= 0.008] and over time compared to patients with B-cell recovery (Fig. A). Patients with long-term B cell aplasia also had lower pre-infusion absolute neutrophil counts (2.3K/µL (IQR 1.4-4.15) vs. 3.5K/µL (IQR 2.8-4.2); P<0.001) and higher baseline CAR-HEMATOTOX scores [2 (IQR 1-3.25) vs 1 (IQR 0-1)], consistent with poor baseline hematopoietic reserve (Rejeski, Blood 2021). While disease-related mortality did not significantly differ between groups, non-relapse mortality was markedly higher in patients with long-term B-cell aplasia due to infection: all 8 patient deaths in the aplasia group were due to infections occurring beyond day 30 post-infusion, with 6 of the 8 deaths due to COVID-19. However, no patients in the B-cell recovery group died of late infection (Fig. B). Conclusions: Long term B-cell aplasia is hypothesized to represent ongoing CAR T-cell activity against normal B-cells. However, our results demonstrate that B-cell aplasia is associated with low baseline hematopoietic reserve and subsequent poor immune reconstitution of multiple lineages including B-cells, T-cells, and myeloid cells. Further studies are warranted to assess whether poor immune reconstitution and B-cell aplasia are related to long term CAR T-cell activity or other processes. These patients are at higher risk for non-relapse mortality from infection, and mitigation strategies are needed.

ABSTRACT The authors aimed to assess the impact of a family caregiver support intervention on caregiver burden and hospital readmission before and during the COVID-19 pandemic. By adopting a quasi-experimental design with no randomization, caregivers (n = 65) received a 90-day home visitation caregiver support intervention before the COVID-19 pandemic and caregivers (n = 41) received a 90-day phone-only visitation caregiver support intervention during the COVID-19 pandemic. Caregiver burden was collected in a survey, and hospital readmission of the care recipient was collected by hospital data. The results of a repeated-measures ANOVA demonstrated that participants of a family caregiver support intervention during the COVID-19 pandemic improved their caregiver burden statistically significantly more than those who received the intervention before the pandemic. There were no significant differences in hospital readmissions before or during the COVID-19 pandemic. The study demonstrates the efficacy of family caregiver support interventions over the phone during a pandemic.

Medical and surgical education is an expansive field fraught with many challenges. Technology such as virtual reality could be a new venue that can offer a solution to improve surgical training. The objective of this prospective, blinded study was to evaluate virtual reality as a training model for orthopedic surgery and surgical training at large. Fourth-year medical students with novice skills volunteered to participate in this observer-blinded 1:1 randomized controlled trial. They had no prior experience in tibia intramedullary nail (IMN) surgery. They were randomized into traditional technique guide education and virtual reality. The participants were timed on their mock surgery, and a blinded observer was utilized to subjectively grade their performance throughout the procedure using the Global Assessment 5-point Rating Scale and Procedure-Specific Checklist. Thirty-eight participants were recruited and randomized into virtual reality (19) and traditional (19) groups. There were trends in all categories favoring the virtual reality group. The VR group had improved time to completion (9.6 minutes vs 12.2 minutes, P = 0.034) and reduced need for corrections within the mock procedure (2.2 vs 2.5; P = 0.05). Virtual reality training was more effective than traditional training in learning and completing the steps of the tibia IMN surgery for novice medical students. Virtual reality training may be a useful method to augment orthopedic education and surgical training.

Numerous studies have demonstrated the clinical benefits of continuous glucose monitoring (CGM) in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) who are treated with intensive insulin regimens. Based on this evidence, CGM is now a standard of care for individuals within these diabetes populations and widely covered by commercial and public insurers. Moreover, recent clinical guidelines from the American Diabetes Association and American Association of Clinical Endocrinology now endorse CGM use in individuals treated with nonintensive insulin regimens. However, despite increasing evidence supporting CGM use for individuals treated with less-intensive insulin therapy or noninsulin medications, insurance coverage is limited or nonexistent. This narrative review reports key findings from recent randomized, observational, and retrospective studies investigating use of CGM in T2D individuals treated with basal insulin only and/or noninsulin therapies and presents an evidence-based rationale for expanding access to CGM within this population.

BackgroundHand infections are heterogeneous, and some may undergo successful outpatient management. There are no strict guidelines for determining which patients will likely require inpatient admission for successful treatment, and many patients succeed with outpatient therapy. We sought to determine risk factors for failed outpatient management of cellulitic hand infections.MethodsWe performed a retrospective review of patients who presented to the Emergency Department (ED) for hand cellulitic infections over five years, from 2014 to 2019. Vital signs, lab markers, Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Measure (ECM), and antibiotic use were investigated. Discharge from the ED without subsequent admission was considered an outpatient success, while admission within 30 days of the prior visit was considered a failure. Continuous variables were compared with Welch's t test, and categorical data with Fisher's exact tests. Multivariable logistic regression was performed on comorbidities. Multiple testing adjustment was performed on p-values to generate q-values.ResultsOutpatient management was attempted for 1,193 patients. 31 (2.6%) infections failed treatment, and 1,162 (97.4%) infections succeeded. Attempted outpatient treatment was 97.4% successful. Multivariable analysis demonstrated higher odds of failure with renal failure according to both CCI (OR 10.2, p < 0.001, q = 0.002) and ECM (OR 12.63, p = 0.003, q = 0.01) and with diabetes with complications according to the CCI (OR 18.29, p = 0.021, q = 0.032).ConclusionsOutpatient treatment failure was higher in patients with renal failure and complicated diabetes. These patients require a high index of suspicion for outpatient failure. These comorbidities should influence consideration for inpatient therapy though most patients can undergo successful treatment as outpatients.Level of evidenceLevel III.