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AbstractBackgroundIdentifying patient‐, facility‐, and environment‐level factors that influence the initiation and retention of comprehensive lifestyle management interventions (CLMI) for urban and rural Veterans could improve obesity treatment and reach at Veterans Affairs (VA) facilities.AimsThis study identified factors at these various levels that predicted treatment engagement, retention, and weight management among urban and rural Veterans.MethodsA retrospective cohort study of 631,325 Veterans was designed using VA databases to identify Veterans with class II and III obesity during 2015–2017. Primary outcomes were initiation of CLMI, bariatric surgery, or obesity pharmacotherapy within 1 year of index date. Secondary outcomes included treatment retention and successful weight loss. Generalized linear mixed models were used to evaluate the relationships between factors and obesity‐related outcomes, with rurality differences assessed through interaction terms.ResultsPatient characteristics associated with increased odds of initiating CLMI included female sex (p < 0.001), black race (p < 0.001), sleep apnea (p < 0.001), mood disorder (p < 0.001), and use of medications associated with weight loss (p < 0.001) or weight gain (p < 0.001). Facility use of telehealth was associated with greater odds of CLMI initiation in urban Veterans (p < 0.001) but lower retention in both populations (p = 0.003). Routine consideration of pharmacotherapy was associated with higher CLMI initiation. Environmental characteristics associated with increased odds of CLMI initiation included percent of population foreign born (OR = 1.03 per 10% increase; p < 0.001), percent black (p < 0.001), and high walkability index (p < 0.001). The relationship between total population and CLMI initiation differed by rurality, as greater population was associated with lower odds of CLMI initiation in urban areas (OR: 0.99 per 1000 population; p < 0.001), but higher odds in rural areas (OR:1.01, p = 0.01). Veterans in the south were less likely to initiate CLMI and had lower retention (p < 0.001).ConclusionTreatment and retention of CLMI among Veterans remain low, highlighting areas for improvement to expand its reach both urban and rural Veterans.

AbstractBackgroundSome patients express concerns regarding receipt of allogeneic blood transfusions from donors potentially vaccinated against SARS‐CoV‐2 (COVID‐19). However, limited information exists about patients' expression of these concerns or how to address them during the blood transfusion consent process. In this study, we describe our experience of working collaboratively with patients with vaccine‐related transfusion concerns prior to elective surgery, summarizing treatment decisions and clinical outcomes.Study Design and MethodsThis observational descriptive study includes patients seen in our Bloodless Medicine and Surgery clinic between June 2022 and June 2024 for vaccine‐related transfusion concerns prior to elective surgery. A shared decision‐making framework was employed to foster conversation, share information, provide reassurance, reconcile conflict, and match preferences with available care options. Patient characteristics, treatment decisions, and surgical outcomes were reviewed and summarized.ResultsThirty‐five patients were included, with median (1st, 3rd quartile) age of 61 (53, 69) years. Cardiac surgery was the most common type of surgery (29%). Twelve patients (34%) were anemic preoperatively, and all received preoperative treatment. After discussion with a Bloodless Medicine specialist, 24 (68.6%) decided to consent to the use of all blood products, 5 (14.3%) accepted only red blood cells, and 6 (17.1%) declined all blood products. Among 28 patients undergoing surgery, only 4 (14%) received allogeneic transfusion perioperatively.ConclusionMany patients concerned about the vaccination status of blood donors may ultimately consent to allogeneic blood products after shared decision‐making with a Bloodless Medicine specialist, highlighting the importance of patient empowerment and collaborative care.

ImportanceAlthough prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown improved sensitivity and specificity compared with conventional imaging for the detection of biochemical recurrent (BCR) prostate cancer, the long-term outcomes of a widespread shift in imaging are unknown.ObjectiveTo estimate long-term outcomes of integrating PSMA-PET into the staging pathway for recurrent prostate cancer.Design, Setting, and ParticipantsThis decision analytic modeling study simulated outcomes for patients with BCR following initial definitive local therapy. Inputs used were from the literature and a retrospective cohort study conducted at 2 institutions. The base case analysis assumed modest benefits of earlier detection and treatment, and scenario analyses considered prostate-specific antigen (PSA) level at imaging and different outcomes of earlier vs delayed treatment. The analysis was performed between April 1, 2023, and May 1, 2024.Exposures(1) Immediate PSMA-PET imaging, (2) conventional imaging (computed tomography and bone scan [CTBS]) followed by PSMA-PET if CTBS findings were negative or equivocal, and (3) CTBS alone.Main Outcomes and MeasuresThe main outcomes were detection of metastases, deaths from prostate cancer, and life-years and quality-adjusted life-years (QALYs) gained.ResultsThe model estimated that per 1000 simulated patients with BCR (assumed median age, 66 years), PSMA-PET is expected to diagnose 611 (95% uncertainty interval [UI], 565-656) patients with metastasis compared with 630 (95% UI, 586-675) patients diagnosed using CTBS followed by PSMA-PET and 297 (95% UI, 202-410) patients diagnosed using CTBS alone. Moreover, the estimated number of prostate cancer deaths was 512 (95% UI, 472-552 deaths) with PSMA-PET, 520 (95% UI, 480-559 deaths) with CTBS followed by PSMA-PET, and 587 (95% UI, 538-632 deaths) with CTBS alone. Imaging with PSMA-PET yielded the highest number of QALYs, which were 824 (95% UI, 698-885) higher than CTBS. These results differed by PSA level at the time of testing, with the highest incremental life-years and QALYs and lowest number of deaths from prostate cancer among patients with PSA levels of at least 5.0 ng/mL. Finally, the estimates were sensitive to the expected benefit of initiating therapy for recurrent prostate cancer earlier in the disease course.Conclusions and RelevanceThe results of this decision-analytic model suggest that upfront PSMA-PET imaging for the evaluation of BCR is expected to be associated with reduced cancer mortality and gains in life-years and QALYs compared with the conventional imaging strategy, assuming modest benefits of earlier detection and treatment.

Background: There are few and controversial results on 24,25(OH)2D and FGF23 acute changes following supplementation with cholecalciferol. Methods: Twenty-seven subjects with 25(OH)D < 30 ng/mL were randomized into three groups to receive a single oral dose of 25,000 I.U. or 600,000 I.U. of cholecalciferol or placebo, respectively. We measured 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, and FGF23 levels at baseline and after 72 h. The 1,25(OH)2D/25(OH)D, 1,25(OH)2D/24,25(OH)2D, and 24,25(OH)2D/25(OH)D ratios were also calculated. Results: There was an increase in 25(OH)D and 1,25 (OH)2D following both doses of cholecalciferol. In the group administered 600,000 I.U., there was a significant increase in the delta changes in 25(OH)D and 1,25(OH)2D compared to the placebo and in the delta 24,25(OH)D2 compared to the placebo and 25,000 I.U. groups (all p < 0.05). A decrease in both the 1,25(OH)2D/25(OH)D and 1,25(OH)2D/24,25(OH)2D ratio (all p < 0.05) was observed in the 600,000 I.U. group. FGF23 values significantly increased only in the group administered 600,000 I.U. Conclusions: 25(OH)D and 1,25(OH)D levels significantly increased following 600,000 IU cholecalciferol administration compared to 25,000 I.U. and placebo. Following the massive administration of cholecalciferol, the CYP24A1 enzyme is actively involved in catabolism, thus, avoiding toxic effects.

Background: Cardiometabolic disease (CMD) disproportionately affects African American/Black (AA) and Latino communities. CMD disparities are exacerbated by their underrepresentation in clinical trials for CMD treatments including nutritional interventions. The study aimed to (1) form a precision nutrition community consultant panel (PNCCP) representative of Latino and AA communities in Los Angeles to identify barriers and facilitators to recruitment and retention of diverse communities into nutrition clinical trials and (2) develop culturally informed strategies to improve trial diversity. Methods: A deliberative community engagement approach was used to form a PNCCP for the Nutrition for Precision Health (NPH) trial, part of the of the All of Us research initiative. The PNCCP included individuals that provide services for Latino and AA communities who met during 11 virtual sessions over 1 year. Discussion topics included enhancing recruitment and cultural acceptance of the NPH trial. We summarized CCP recommendations by theme using an inductive qualitative approach. Results: The PNCCP included 17 adults (35% AA, 47% Latino). Four thematic recommendations emerged: reducing structural barriers to recruitment, the need for recruitment materials to be culturally tailored and participant-centered, community-engaged trial recruitment, and making nutrition trial procedures inclusive and acceptable. We outlined the study response to feedback, including the constraints that limited implementation of suggestions. Conclusion: This study centers community voices regarding the recruitment and retention of AA and Latino communities into a nutrition clinical trial. It highlights the importance of community engagement early on in protocol development and maintaining flexibility to enhance inclusion of diverse communities in nutrition clinical trials.

As a treatment for the widely spread cardiovascular diseases (CVD), bypass vascular grafts have room for improvement in terms of mechanical property match with native arteries. A 3D‐printed nozzle is presented, featuring unique internal structures, to extrude artificial vascular grafts with a flower‐mimicking geometry. The multilayer‐structured graft wall allows the inner and outer layers to interfere sequentially during lateral expansion, replicating the nonlinear elasticity of native vessels. Both experiment and simulation results verify the necessity and benefit of the flower‐mimicking structure in obtaining the self‐toughening behavior. The gelation study of natural polymers and the utilization of sacrificial phase enables the smooth extrusion of the multiphase conduit, where computer‐assisted image analysis is employed to quantify manufacturing fidelity. The cell viability tests demonstrate the cytocompatibility of the gelatin methacryloyl (GelMA)/sodium alginate grafts, suggesting potential for further clinical research with further developments. This study presents a feasible approach for fabricating bypass vascular grafts and inspires future treatments for CVD.

PURPOSE On the basis of the results of the ZUMA-3 trial, brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor T-cell therapy, gained US Food and Drug Administration approval in October 2021 for adults with relapsed/refractory (R/R) B-cell ALL (B-ALL). We report outcomes of patients treated with brexu-cel as a standard therapy. METHODS We developed a collaboration across 31 US centers to study adults with B-ALL who received brexu-cel outside the context of a clinical trial. Data were collected retrospectively from October 2021 to October 2023. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). RESULTS At the time of data lock, 204 patients had undergone apheresis and 189 were infused. Median follow-up time was 11.4 months. Forty-two percent of patients received brexu-cel in morphologic remission and would have been ineligible for participation in ZUMA-3. After brexu-cel, 151 achieved complete remission (CR), of which 79% were measurable residual disease (MRD) negative remissions. Median progression-free survival (PFS) was 9.5 months and median overall survival was not reached. Grade 3-4 CRS or ICANS occurred in 11% and 31%, respectively. In multivariable analysis, patients receiving consolidative hematopoietic cell transplantation (HCT; hazard ratio, 0.34 [95% CI, 0.14 to 0.85]) after brexu-cel had superior PFS compared with those who did not receive any consolidation or maintenance therapy. CONCLUSION Similar to ZUMA-3, high rates of MRD-negative CR were observed after brexu-cel treatment for R/R B-ALL. The use of HCT as consolidation after brexu-cel resulted in improved PFS.

Abstract Introduction: Pragmatic trials aim to speed translation to practice by integrating study procedures in routine care settings. This study evaluated implementation outcomes related to clinician and patient recruitment and participation in a trial of community paramedicine (CP) and presents successes and challenges of maintaining pragmatic study features. Methods: Adults in the pre-hospital setting, emergency department (ED), or hospital being considered for referral to the ED/hospital or continued hospitalization for intermediate-level care were randomized 1:1 to CP care or usual care. Referral and enrollment data were tracked administratively, and patient characteristics were abstracted from the electronic health record (EHR). Enrolled patients completed baseline surveys, and a subset of intervention patients were interviewed. All CPs and a sample of clinicians and administrators were invited to complete a survey and interview. Results: Between January 2022 and February 2023, 240 enrolled patients (42% rural) completed surveys, and 22 completed an interview; 63 staff completed surveys and 20 completed an interview. Ninety-three clinicians in 27 departments made at least one referral. Factors related to referrals included program awareness and understanding the CP practice scope. Most patients were enrolled in the hospital, but characteristics were similar to the primary care population and included older and medically complex patients. Challenges to achieving representativeness included limited EHR infrastructure, constraints related to patient consenting, and clinician concerns about patient randomization disrupting preferred care. Conclusion: Future pragmatic trials in busy clinical settings may benefit from regulatory policies and EHR capabilities that allow for real-world study conduct and representative participation. Trial registration: NCT05232799.