Enhancing team communication to improve implementation of a supervised walking program for hospitalized veterans: Evidence from a multi-site trial in the Veterans Health Administration.

INTRODUCTION: The timely translation of evidence-based programs into real-world clinical settings is a persistent challenge due to complexities related to organizational context and team function, particularly in inpatient settings. Strategies are needed to promote quality improvement efforts and implementation of new clinical programs. OBJECTIVE: This study examines the role of CONNECT, a complexity science-based implementation intervention to promote team readiness, for enhancing implementation of the 'Assisted Early Mobility for Hospitalized Older Veterans' program (STRIDE), an inpatient, supervised walking program. DESIGN: We conducted a stepped-wedge cluster randomized trial using a convergent mixed-methods design. Within each randomly assigned stepped-wedge sequence, Veterans Affairs Medical Centers (VAMCs) were randomized to receive standardized implementation support only or additional training via the CONNECT intervention. Data for the study were obtained from hospital administrative and electronic health records, surveys, and semi-structured interviews with clinicians before and after implementation of STRIDE. SETTING: Eight U.S. VAMCs. PARTICIPANTS: Three hundred fifty-three survey participants before STRIDE implementation and 294 surveys after STRIDE implementation. Ninety-two interview participants. INTERVENTION: CONNECT, a complexity-science-based intervention to improve team function. MAIN OUTCOME MEASURES: The implementation outcomes included STRIDE reach and fidelity. Secondary outcomes included validated measures of team function (i.e., team communication, coordination, role clarity). RESULTS: At four VAMCs randomized to CONNECT, reach was higher (mean 12.4% vs. 3.8%), and fidelity was similar to four non-CONNECT VAMCs. VAMC STRIDE delivery teams receiving CONNECT reported improvements in team function domains, similar to non-CONNECT VAMCs. Qualitative findings highlight CONNECT's impact and the influence of team characteristics and contextual factors, including team cohesion, leadership support, and role clarity, on reach and fidelity. CONCLUSION: CONNECT may promote greater reach of STRIDE, but improvement in team function among CONNECT VAMCs was similar to improvement among non-CONNECT VAMCs. Qualitative findings suggest that CONNECT may improve team function and implementation outcomes but may not be sufficient to overcome structural barriers related to implementation capacity.

Integration of individual preclinical and clinical anti-infective PKPD data to predict clinical study outcomes.

The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination therapy in carbapenem-resistant Gram-negative infections. The aim of this reverse translational study was to integrate all individual preclinical and clinical pharmacokinetic-pharmacodynamic (PKPD) data from the AIDA trial in a pharmacometric framework to explore whether individualized predictions of bacterial burden were associated with the trial outcomes. The compiled dataset included for each of the 207 patients was (i) information on the infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, and fitness in a murine model), (ii) colistin plasma concentrations and colistin and meropenem dosing history, and (iii) disease scores and demographics. The individual information was integrated into PKPD models, and the predicted change in bacterial count at 24 h for each patient, as well as patient characteristics, was correlated with clinical outcomes using logistic regression. The in vivo fitness was the most important factor for change in bacterial count. A model-predicted growth at 24 h of ≥2-log10 (164/207) correlated positively with clinical failure (adjusted odds ratio, aOR = 2.01). The aOR for one unit increase of other significant predictors were 1.24 for SOFA score, 1.19 for Charlson comorbidity index, and 1.01 for age. This study exemplifies how preclinical and clinical anti-infective PKPD data can be integrated through pharmacodynamic modeling and identify patient- and pathogen-specific factors related to clinical outcomes - an approach that may improve understanding of study outcomes.

Review of venipuncture and intravenous catheterization techniques in pigs.

The number of companion pigs in the US is increasing, as is the frequency with which they present to primary companion care practices. However, pigs are often an understudied species in veterinary curricula, and many students graduate from veterinary school with minimal porcine handling experience. Coupled with the poor peripheral vascular access associated with pigs, this presents a challenge for many new graduates and other primary care veterinarians seeking to improve their knowledge of porcine handling, anatomy, and medical care. Furthermore, much of the available veterinary literature regarding porcine venous access is dated, limited to technical notes, or inaccessible to many primary care veterinarians. This review aims to supplement this lack of knowledge by discussing techniques in restraint, sedation, venipuncture, and catheterization of companion pigs as a reference for veterinarians and researchers alike.

Perioperative Patient-Initiated Communication in Gender-Affirming Mastectomy.

Background: Gender-affirming mastectomy (GAM) improves the psychosocial functioning and quality of life of transgender and non-binary (TGNB) individuals. However, the perioperative period is often marked by emotional stress, concerns about surgical outcomes, and physical discomfort. While inpatient procedures provide multiple opportunities to engage with and educate patients, outpatient surgeries, such as GAM, pose a unique challenge as patients are followed for <24 h postoperatively. Given the heightened emotional and psychological distress related to gender dysphoria TGNB individuals often experience, addressing these gaps can significantly improve outcomes. This study aims to characterize patient and surgical characteristics associated with patient-initiated communication (PIC) frequency in this population. Methods: A single-center retrospective review of TGNB patients undergoing GAM from February 2018 to November 2022 was conducted. Demographics, surgical characteristics, and frequency of and reasons for perioperative PIC (30 days before and after surgery) were recorded. The primary outcome was the incidence of perioperative PIC. The secondary outcomes included (1) the rationale for PIC and (2) patient and surgical characteristics associated with PIC. Results: A total of 352 patients were included. Of these, 285 (74.6%) initiated communication in the perioperative period, totaling 659 PICs. The median age was 25.0 (interquartile range [IQR]: 9.0) years. The median body mass index (BMI) was 28.5 (IQR: 8.5) kg/m2. The mean number of PICs was 0.7 ± 1.3 preoperatively and 1.3 ± 1.7 postoperatively (p < 0.001). The most frequent preoperative PIC subjects were administrative issues (AI; n = 66, 30.7%), preoperative requirements (n = 43, 20.0%), and cost and insurance (n = 33, 15.0%). The most frequent postoperative PIC subjects were wound care (n = 77, 17.3%), AI (n = 70, 15.0%), activity restrictions (n = 60, 13.5%), drainage (n = 56, 12.6%), and swelling (n = 37, 8.3%). Collectively, older patients (ß = 0.234, p = 0.001), those with a history of major depressive disorder or generalized anxiety disorder (2.4 ± 3.0 vs. 1.7 ± 1.9; p = 0.019), and those without postoperative drains (n = 16/17, 94.1% vs. n = 236/334, 70.7%; p = 0.025) engaged in higher levels of PIC. There were no significant associations between other patient characteristics, perioperative details, or complications and PIC frequency. Conclusions: Perioperative PIC is prevalent among the majority of GAM patients at our institution, with age, psychiatric diagnosis, and postoperative drain use identified as significant predictors. To mitigate PIC frequency, it is crucial to ensure adequate support staffing and provide comprehensive postoperative instructions, particularly concerning activity restrictions and drainage management. These interventions may reduce PICs in high-volume centers. Further research should investigate targeted interventions to further support TGNB patients during the perioperative period.

DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases.

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes.

Evolution and engineering of pathways for aromatic O-demethylation in Pseudomonas putida KT2440.

Biological conversion of lignin from biomass offers a promising strategy for sustainable production of fuels and chemicals. However, aromatic compounds derived from lignin commonly contain methoxy groups, and O-demethylation of these substrates is often a rate-limiting reaction that influences catabolic efficiency. Several enzyme families catalyze aromatic O-demethylation, but they are rarely compared in vivo to determine an optimal biocatalytic strategy. Here, two pathways for aromatic O-demethylation were compared in Pseudomonas putida KT2440. The native Rieske non-heme iron monooxygenase (VanAB) and, separately, a heterologous tetrahydrofolate-dependent demethylase (LigM) were constitutively expressed in P. putida, and the strains were optimized via adaptive laboratory evolution (ALE) with vanillate as a model substrate. All evolved strains displayed improved growth phenotypes, with the evolved strains harboring the native VanAB pathway exhibiting growth rates ∼1.8x faster than those harboring the heterologous LigM pathway. Enzyme kinetics and transcriptomics studies investigated the contribution of selected mutations toward enhanced utilization of vanillate. The VanAB-overexpressing strains contained the most impactful mutations, including those in VanB, the reductase for vanillate O-demethylase, PP_3494, a global regulator of vanillate catabolism, and fghA, involved in formaldehyde detoxification. These three mutations were combined into a single strain, which exhibited approximately 5x faster vanillate consumption than the wild-type strain in the first 8 h of cultivation. Overall, this study illuminates the details of vanillate catabolism in the context of two distinct enzymatic mechanisms, yielding a platform strain for efficient O-demethylation of lignin-related aromatic compounds to value-added products.

Facilitating active learning of sectional anatomy with technology-enhanced small-group tasks: Assessment of knowledge gains, technology usability, and students' perceptions.

Learning 2D sectional anatomy facilitates the comprehension of 3D anatomical structures, anatomical relationships, and radiological anatomy. However, the efficacy of technology-enhanced collaborative instructional activities in sectional anatomy remains unclear, especially if theoretical frameworks, namely the Cognitive Theory of Multimedia Learning (CTML), are applied in instructional design. Thus, this study compared the educational impact of distinct 45-min-long technology-enhanced collaborative learning tasks in sectional anatomy. A sample of 115 first-year medical students was randomly divided into three experimental groups that used different supporting technologies to learn the sectional anatomy of the chest: IMAIOS e-learning platform and Microsoft Surface Hub (n = 37); anatomage table (n = 38); anatomage table with CTML-based presets (n = 40). Prelearning and postlearning tests revealed that significant knowledge gains in sectional anatomy were obtained by all groups even though no inter-group differences were found. Moreover, a five-point Likert scale questionnaire showed that the learning session was highly valued by all participants and that users of the anatomage with CTML-based presets reported higher enjoyment than users of the IMAIOS system (mean difference = 0.400; p = 0.037). In addition, students using the IMAIOS system and the anatomage with CTML-based presets provided System Usability Scale (SUS) scores of 67.64 and 67.69, respectively, reaching the benchmark of usability. By contrast, students using the anatomage table without presets awarded a SUS score of 64.14. These results suggest that the integration of multimedia technologies in anatomy teaching and learning should be grounded on CTML principles of instructional design. Otherwise, students' perceptions of ed-tech usability are potentially hindered.

Opioid-related xylazine toxicity manifesting as myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema.

This article provides a report of a case of organ dysfunction, myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema after a patient's use of xylazine and fentanyl. Within the US opioid epidemic, xylazine is emerging as a troubling national sub-story. The prevalence of xylazine within illicitly manufactured opioids and the proportion of opioid-involved overdose deaths with detected xylazine are rising dramatically, the latter increasing 276% between 2019 and 2022. A 27-year-old woman with opioid use disorder, active intravenous drug use, and prior bacteremia presented to our institution's emergency department (ED) with left lower extremity pain and associated weakness, new acute bilateral hearing loss, multiple electrolyte derangements, and cerebral infarcts followed by cerebral edema, leading to an emergent sub-occipital decompressive craniectomy and placement of an external ventricular drain. A definitive mechanism was not determined; however, we hypothesized that xylazine toxicity played a role in her clinical presentation, which could have future clinical implications, including the possibility to incorporate xylazine as part of toxicology screens.

Topical gabapentin and its relation to cutaneous innervation in symptomatic lymphocytic primary cicatricial alopecia.

In this pilot study, participants with symptomatic lymphocytic primary cicatricial alopecia applied 6% topical gabapentin solution twice daily to affected areas for 12 weeks. There was a significant reduction in symptoms, but no pronounced effect on nerve fibre density or neuropeptide expression.

Task-irrelevant semantic relationship between objects and scene influence attentional allocation.

Recent behavioral evidence suggests that the semantic relationships between isolated objects can influence attentional allocation, with highly semantically related objects showing an increase in processing efficiency. This semantic influence is present even when it is task-irrelevant (i.e., when semantic information is not central to the task). However, given that objects exist within larger contexts, i.e., scenes, it is critical to understand whether the semantic relationship between a scene and its objects continuously influence attention. Here, we investigated the influence of task-irrelevant scene semantic properties on attentional allocation and the degree to which semantic relationships between scenes and objects interact. Results suggest that task-irrelevant associations between scenes and objects continuously influence attention and that this influence is directly predicted by the perceived strength of semantic associations.

Identification of a copper-responsive small molecule inhibitor of uropathogenic Escherichia coli.

Urinary tract infections (UTIs) are a major global health problem and are caused predominantly by uropathogenic Escherichia coli (UPEC). UTIs are a leading cause of prescription antimicrobial use. Incessant increase in antimicrobial resistance in UPEC and other uropathogens poses a serious threat to the current treatment practices. Copper is an effector of nutritional immunity that impedes the growth of pathogens during infection. We hypothesized that copper would augment the toxicity of select small molecules against bacterial pathogens. We conducted a small molecule screening campaign with a library of 51,098 molecules to detect hits that inhibit a UPEC ΔtolC mutant in a copper-dependent manner. A molecule, denoted as E. coli inhibitor or ECIN, was identified as a copper-responsive inhibitor of wild-type UPEC strains. Our gene expression and metal content analysis results demonstrate that ECIN works in concert with copper to exacerbate Cu toxicity in UPEC. ECIN has a broad spectrum of activity against pathogens of medical and veterinary significance including Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Subinhibitory levels of ECIN eliminate UPEC biofilm formation. Transcriptome analysis of UPEC treated with ECIN reveals induction of multiple stress response systems. Furthermore, we demonstrate that L-cysteine rescues the growth of UPEC exposed to ECIN. In summary, we report the identification and characterization of a novel copper-responsive small molecule inhibitor of UPEC.IMPORTANCEUrinary tract infection (UTI) is a ubiquitous infectious condition affecting millions of people annually. Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of UTI. However, UTIs are becoming increasingly difficult to resolve with antimicrobials due to increased antimicrobial resistance in UPEC and other uropathogens. Here, we report the identification and characterization of a novel copper-responsive small molecule inhibitor of UPEC. In addition to E. coli, this small molecule also inhibits pathogens of medical and veterinary significance including Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus.

Robert Gross MD and the Birth of Pediatric Heart Surgery.

Robert Gross performed the first repair of a patent ductus arteriosus in 1938. His life and career were dedicated to the advancement of vascular, cardiac, pediatric surgery, and the unrelenting care of his patients.

Seizure clusters, treatment patterns, and healthcare resource utilization in patients with epilepsy: A Wisconsin-based claims analysis.

BACKGROUND: Seizure clusters are underresearched and associated with adverse outcomes in patients with epilepsy. This study was a noninterventional, retrospective claims-based analysis using the Wisconsin Health Information Organization (WHIO) All-Payer Claims Database to characterize the epilepsy population in Wisconsin, with a focus on prevalence, treatment patterns, and healthcare resource utilization (HCRU) in patients with seizure clusters prior to the introduction of nasal spray rescue medications. This timeframe allows characterization of a historical baseline for future comparisons with newer treatments. METHODS: Four cohorts were defined: (1) all-epilepsy (all patients with epilepsy); and subcohorts of: (2) patients receiving a monotherapy antiseizure medication (ASM); (3) patients receiving ASM polytherapy; and (4) patients treated for seizure clusters (ie, those taking rescue medications and ≥ 1 ASM). Primary outcomes were HCRU over a 12-month follow-up period, which were descriptively analyzed. RESULTS: Between 2017 and 2019, 16,384 patients were included in the all-epilepsy cohort; 11,688 (71.3 %) were on monotherapy, 3,849 (23.5 %) were on polytherapy, and 526 (3.2 %) were treated for seizure clusters. Twelve-month retentions to the ASM treatments were 46.7 % (7,895/16,904) in the all-epilepsy cohort, and 40.0 % (4,679/11,688) and 40.1 % (1,544/3,849) in the monotherapy and polytherapy subcohorts, respectively. Rescue medication prescriptions were obtained 1,029 times by the 526 patients in the treated seizure cluster subcohort, with infrequent refill rates (mean 1.6-1.9 times/year). A higher proportion of patients in the treated seizure cluster subcohort had epilepsy-related outpatient visits (89.7 %), other visits (71.3 %), and hospitalizations (25.3 %) than patients in the monotherapy (72.2 %, 50.2 %, 19.3 %, respectively) and polytherapy (83.3 %, 63.3 %, 22.8 %, respectively) subcohorts. Mean (standard deviation) all-cause ($114,717 [$231,667]) and epilepsy-related ($76,134 [$204,930]) costs over 12 months were higher in the treated seizure cluster subcohort than the monotherapy ($89,324 [$220,181] and $30,745 [$145,977], respectively) and polytherapy ($101,506 [$152,931] and $49,383 [$96,285], respectively) subcohorts. CONCLUSIONS: Patients treated for seizure clusters incurred higher all-cause and epilepsy-related costs and epilepsy-related HCRU than other subcohorts and had infrequent rescue medication refills. The findings of this analysis highlight the need for appropriate treatment for those patients with epilepsy experiencing seizure clusters. The effect of newer rescue medications to alter these findings will be explored in a follow-up study. Regardless, specialist providers with expertise in treating refractory epilepsy and seizure cluster patients may help to reduce the burden of seizure clusters.

Design and baseline characteristics of the Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) randomized trial.

BACKGROUND AND HYPOTHESIS: Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney, and cardiovascular outcomes in patients with CKD and T2D in two Phase 3 outcome trials. The FIND-CKD study investigates the effect of finerenone in adults with CKD without diabetes. METHODS: FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled Phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin-creatinine ratio (UACR) of ≥ 200 to ≤3500 mg/g and eGFR ≥ 25 to <90 mL/min/1.73 m2 receiving a maximum tolerated dose of a renin-angiotensin-system (RAS) inhibitor were randomized 1:1 to once daily placebo or finerenone 10 or 20 mg depending on eGFR above or below 60 mL/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to Month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure, or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety. RESULTS: Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 mL/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%), and calcium channel blockers by 794 (50.1%). SGLT2 inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 vs 46.8 mL/min/1.73 m2) and slightly higher median UACR (871.9 vs 808.3 mg/g) compared to those not using SGLT2 inhibitors at baseline. CONCLUSIONS: FIND-CKD is the first Phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology.

NUAK: never underestimate a kinase.

NUAK1 and NUAK2 belong to a family of kinases related to the catalytic α-subunits of the AMP-activated protein kinase (AMPK) complexes. Despite canonical activation by the tumour suppressor kinase LKB1, both NUAKs exhibit a spectrum of activities that favour tumour development and progression. Here, we review similarities in structure and function of the NUAKs, their regulation at gene, transcript and protein level, and discuss their phosphorylation of specific downstream targets in the context of the signal transduction pathways and biological activities regulated by each or both NUAKs.

A Health-Related Quality of Life Measure for Patients Who Undergo Minimally Invasive Glaucoma Surgery.

PURPOSE: To develop a standardized patient-reported outcome measure to assess the impact of glaucoma and treatment, including minimally invasive glaucoma surgery (MIGS), on health-related quality of life (HRQOL). DESIGN: Observational study before and after concomitant cataract and FDA-approved implantable MIGS device surgery to provide information on the measure's performance in assessing HRQOL. METHODS SETTING: Survey administration was done by electronic patient-reported outcomes (ePRO) application to patients at multiple sites on a computer, iPad, or similar device. PATIENT POPULATION: One hundred eighty-four adults completed a baseline survey, 124 completed a survey 3 months after surgery, and 106 completed the 1-month test-retest reliability survey. The age range was 37-89, and the average age was 72. Most of the respondents were female (57%), non-Hispanic White (81%), and had a college degree (56%). MAIN OUTCOME MEASURES: The Glaucoma Outcomes Survey (GOS) includes 42 questions assessing functional limitations (27 items), vision-related symptoms (7 items), psychosocial issues (7 items) and satisfaction with microinvasive glaucoma surgery (1 item). The three multiple-item scales were scored on a 0-100 range, with a higher score indicating worse health. RESULTS: Internal consistency reliability estimates ranged from 0.75 (vision-related symptoms) to 0.93 (functional limitations) and one-month test-retest intraclass correlations ranged from 0.65 (PROMIS global mental health) to 0.92 (functional limitations). Product-moment correlations among the GOS scales ranged from 0.56 to 0.60. Improvement in visual acuity in the study eye from baseline to the 3-month follow-up was significantly related to improvements in GOS functional limitations (r =0.18, p =0.0485), vision-related symptoms (r = 0.19, p = 0.0386), and psychosocial concerns (r = 0.18, p =0.0503). The highest proportion of responders to treatment was seen for the GOS functional limitations scale (48%), followed by GOS psychosocial issues (21%) and GOS vision-related symptoms (17%). CONCLUSIONS: This study provides initial support for using the GOS instrument in ophthalmic procedures such as MIGS. Further evaluation of the GOS in other samples, including different patient subgroups and clinical settings, will be valuable. The instrument may be useful for evaluations of other treatments for glaucoma.

Understanding pathways from implementation to sustainment: a longitudinal, mixed methods analysis of promising practices implemented in the Veterans Health Administration.

BACKGROUND: The Veterans Health Administration (VHA) is the United States largest learning health system. The Diffusion of Excellence (DoE) program is a large-scale model of diffusion that identifies and diffuses evidence-informed practices across VHA. During the period of 2016-2021, 57 evidence-informed practices were implemented across 82 VHA facilities. This setting provides a unique opportunity to understand sustainment determinants and pathways. Our objective was to characterize the longitudinal pathways of practices as they transition from initial implementation to long-term sustainment at each facility. METHODS: A longitudinal, mixed-methods evaluation of 82 VHA facilities. Eighty-two facility representatives, chosen by leadership as points-of-contact for 57 DoE practices, were eligible for post-implementation interviews and annual sustainment surveys. Primary outcomes (implementation, sustainment), and secondary outcomes (institutionalization, effectiveness, anticipated sustainment) at four time-points were collected. We performed descriptive statistics and directed content analysis using Hailemariam et al.'s factors influencing sustainment. RESULTS: After approximately five years post-implementation (e.g., 2021 sustainment outcomes), of the 82 facilities, about one-third fully sustained their practice compared to one-third that did not fully sustain their practice because it was in a "liminal" stage (neither sustained nor discontinued) or permanently discontinued. The remaining one-third of facilities had missing 2021 sustainment outcomes. A higher percentage of facilities (70%) had inconsistent primary outcomes (changing over time) compared to facilities (30%) with consistent primary outcomes (same over time). Thirty-four percent of facilities with sustained practices reported resilience since they overcame implementation and sustainment barriers. Facilities with sustained practices reported more positive secondary outcomes compared to those that did not sustain their practice. Key factors facilitating practice sustainment included: demonstrating practice effectiveness/benefit, sufficient organizational leadership, sufficient workforce, and adaptation/alignment with local context. Key factors hindering practice sustainment included: insufficient workforce, not able to maintain practice fidelity/integrity, critical incidents related to the COVID-19 pandemic, organizational leadership did not support sustainment of practice, and no ongoing support. CONCLUSIONS: We identified diverse pathways from implementation to sustainment, and our data underscore that initial implementation outcomes may not determine long-term sustainment outcomes. This longitudinal evaluation contributes to understanding impacts of the DoE program, including return on investment, achieving learning health system goals, and insights into achieving high-quality healthcare in VHA.