Citations

Background We analysed the association between host genetic risk scores (GRSs) predicting efavirenz (EFV) plasma levels and exposure and suicidal behaviours in participants in one of several global antiretroviral therapy (ART) clinical trials linked to the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). Methods We conducted a matched case–control study (two controls per case) on suicide or grade-4 suicidal ideation/attempts or depression. Cases and controls were matched by EFV initiation strategy, study, and follow-up time. CYP2B6-based GRS classified participants as extensive, intermediate, or slow metabolisers. EFV and its metabolites (8-hydroxy-EFV and 7-hydroxy-EFV) were measured in plasma. Conditional logistic regression was used to analyse the associations between GRS categories, EFV levels, and suicidal behaviour. Results Among 74 cases and 146 controls, 128 (58.2%) started EFV-containing first-line treatment. Of the treatment-experienced participants, 35% were on EFV at entry. Pre-existing psychiatric conditions and recreational drug-use were more common in cases (16.2%, 25.7%) than in controls (0.7%, 9.6%). On comparing cases to controls, more cases were extensive metabolisers (52% vs. 45%), but there were fewer slow metabolisers (8% vs. 13%). The unadjusted odds ratio (OR) for suicidal behaviour per one more minor allele was 0.76 (95% CI: 0.49–1.18). The OR for being a case vs. a control was 0.57 (95% CI: 0.38–0.86) per doubling of the EFV plasma level. Conclusion CYP2B6-based GRS for cytochrome P450 enzymatic activity appeared not to be associated with suicidal behaviour in individuals living with HIV treated with EFV-containing ART combinations. CYP2B6-based GRS effectively predicted EFV exposure, but suicidal behaviour appeared more likely in extensive (normal) metabolisers.

BACKGROUND: Burnout remains prevalent among anesthesiology residents. Contributing workplace factors include limited control over scheduling, unpredictable hours, critical patient care needs, and other residency challenges. The Family Anesthesia Experience (FAX) is a program designed to educate residents and their support persons on wellness and residency demands. The focus of this multisite study was to evaluate the impact of FAX on first year clinical anesthesiology (CA1, ie, PGY2s) residents’ wellness. METHODS: This was a prospective evaluation study involving 15 US anesthesiology residency programs, 13 of which completed FAX. CA1 wellness was evaluated through surveys assessing perceived stress as the primary outcome, with exploratory outcomes including burnout, depression, psychological wellness, and social support. Additionally, changes in support persons’ understanding and knowledge of residency demands were tracked over time. The study included a historical control group of 302 CA1s (2019-2021) who did not participate in FAX, and an intervention group of 88 CA1s that participated in FAX (2021-2022). Statistical analyses compared changes in metrics between groups using linear mixed models and generalized linear models. RESULTS: Significant reductions in perceived stress were observed in the intervention group at 6 months post-FAX (mean change = –2.14, 95% CI, –3.95 to –0.34; P = .021, effect size = 0.58) relative to the control group, but there was no sustained difference at 12 months. Compared to the control support persons, intervention support persons reported increased understanding of residency demands, with significant improvements at 6 (mean change = 2.80, 95% CI, 1.12–4.48; P = .001, effect size = 0.77) and 12 (mean change = 2.59, 95% CI, 0.12–5.05; P = .039, effect size = 0.71) months. Improvement in support persons’ understanding did not predict changes in CA1 wellness outcomes. First generation physician residents reported lower family support at baseline but showed significant improvements in family support at 6 months (mean change = 3.05 points; 95% CI, 0.25–5.84; P = .033; effect size = 1.23) compared to their non first generation peers. CONCLUSIONS: FAX participation was associated with reduced perceived stress in residents up to 6 months post-intervention. First generation physicians experienced greater improvements in perceived family support compared to their non first generation peers. Our findings suggest that resident wellness may be enhanced by engaging both residents and their support persons in an educational wellness program that outlines the professional expectations and demands of anesthesiology residency training.

Background: Hepatorenal syndrome–acute kidney injury (HRS-AKI) is associated with high mortality in cirrhosis. Recent FDA approval of terlipressin and updated clinical guidance have expanded management options, but real-world practice patterns remain unknown. Methods: We conducted a nationwide survey of U.S. hepatology providers regarding HRS-AKI management practices. The 33-question survey assessed provider demographics, vasoconstrictor selection, treatment timing, and adherence to guideline recommendations. Results: Among 162 respondents, most were hepatologists (94%) at academic centers (83%). Only 11% obtained a nephrology consultation at AKI detection, with 44% waiting until worsening renal function. Terlipressin was available at 80% of institutions but more commonly at academic centers (84% vs. 53%, p =0.003). Consistent with guideline recommendations, 77% of providers initiate vasoconstrictors only after completing a trial of volume expansion (if no renal improvement), particularly in academic centers (80% vs. 60% non-academic, p =0.03). Terlipressin (49%) and midodrine/octreotide (44%) were preferred first-line treatments, with providers at academic centers more likely to use midodrine/octreotide (46% vs. 30%, p =0.008). Mean arterial pressure was used by 62% of providers to guide vasoconstrictor dosing. Most providers (73%) discontinued vasoconstrictor treatment after 4 days if no improvement. Conclusions: Significant variations exist between guideline recommendations and real-world HRS-AKI management, especially first-line treatment choice, treatment monitoring, and nephrology consultation. These findings highlight opportunities to improve guideline implementation and identify areas where practice patterns might inform provider education and future guidance updates.

Background Individuals with intellectual and developmental disabilities experience substantial disparities across the cancer care continuum, including delayed diagnosis, limited access to supportive resources, and heightened psychosocial distress. These challenges are intensified in high-acuity settings where care models are not adapted to their developmental and cognitive needs. Methods We describe an interdisciplinary, patient-centered approach to the care of a 34-year-old patient with developmental delay and metastatic adenocarcinoma. Key strategies emphasized education, preparation, and communication tailored to her cognitive abilities. Collaboration with her family informed effective strategies to reduce distress and improve compliance. Results Tailored interventions – including simplified communication, visual supports, and continuity of providers – improved the patient’s coping, reduced distress, and enabled completion of comprehensive oncologic evaluation and treatment. Conclusions This case demonstrates that structured, interdisciplinary, patient-centered approaches to care can mitigate disparities and support equitable, compassionate care for individuals with intellectual and developmental disabilities facing serious illness.

SUMMARY Goal: The purpose of this study was to enhance access to medication assistance programs (MAPs), which are crucial for providing free medications to patients who cannot afford them. These programs are particularly beneficial for the management of chronic conditions such as diabetes, heart failure, and cancer, for which medication adherence is vital for positive patient outcomes, and cost is a common barrier. Methods: This quality improvement project aimed at optimizing the MAP enrollment process. Interventions included the development of frequently asked questions documents, standardized templates for documentation, establishment of MAP technician office spaces, and standardization of patient referrals. A Mann-Whitney U test and a chi-square test were used to summarize the data in this study. Principal Findings: The project resulted in a 56% increase in new patient enrollments ( p < .01) and a 33% increase in medications provided, with a significant reduction in the average time from patient referral to application approval. Practical Applications: The project improved patient access to MAPs, optimized pharmacy technician resources, and significantly reduced processing times, an important factor in preventing treatment delays and improving patient care. Future plans include expanding the new enrollment process to annual reenrollments, formally establishing the MAP technician within departments, and considering additional pharmacy technician support in response to increasing demand for MAPs.

Abstract Purpose To develop and implement an in‑house treatment‑management platform to improve communication, data accessibility, and task tracking across a radiation oncology department. Methods We developed Capsule, a custom software platform that centralizes patient data from the ARIA oncology information system (Varian Medical Systems, Palo Alto, United States), and integrates it with data from Outlook (Microsoft, Redmond, United States), spreadsheets, and manual inputs. Built using C#, SQL, and the .NET framework, it features a graphical interface in XAML with twelve modular tools to support workflows across a large multi‐modality department. A formal validation, feedback, and maintenance cycle was established. Its impact on workflow efficiency was evaluated using average CarePath task duration before and after implementation, supplemented by user interviews and surveys. Results The Department Schedule, Treatment Planning and On‐Treatment Whiteboard, Spreadsheet, and various workload tracking modules emerged as the most frequently used among dosimetrists surveyed.The Whiteboard module consolidates planning metadata for streamlined workflows. Workload and scheduling modules help distribute tasks fairly. The Department Schedule module centralizes daily role and contact information. The Spreadsheet module allows dosimetrists to identify a reference for unique plans and provides secure access to large exportable tabulated patient data and clinical trends. Other modules support proton down‐time replanning and special procedure physics assignment. One year after Capsule's implementation, most tasks in the external beam radiation therapy workflow experienced a reduction in average duration. Discussion Capsule streamlines workflows by integrating multiple tools into a single platform, supporting urgent scenarios, and improving task hand‐off. Its modular design allows customization to local workflows, but implementation must be guided by institutional oversight and formal quality management to ensure data security and compliance. Conclusion Capsule can provide a solution for improved workflow efficiency, communication, and interdisciplinary coordination. By democratizing access to routine and retrospective data, it supports treatment planning, scheduling, and quality improvement. Ongoing updates are essential as clinical practices evolve.

Abstract Extra-axial chordoma (EAC) is a very rare, malignant tumor with metastatic potential that arises in the extra-axial skeleton and soft tissues. We report the case of a 51-year-old right-handed male with EAC of the left capitate. He underwent capitate resection and wrist arthrodesis utilizing scaphoid autograft with the treatment goal of minimizing risk of tumor recurrence and metastasis while maximizing hand and wrist function. His radiographic outcome demonstrated union of his arthrodesis site. However, 7 months postoperatively, he started experiencing increased hand and wrist pain and was found to have early tumor reoccurrence. Few cases of EAC have been reported in the literature. EAC is typically treated with resection alone, although there is a limited role for chemotherapy and radiation in the setting of locally reoccurring or metastatic disease. Functional outcomes of the affected extremity and survival outcomes vary widely. This is the first report in the literature of EAC of a single carpal bone and describes an innovative technique for definitive surgical treatment of this rare tumor. Utilization of scaphoid autograft for wrist arthrodesis in the setting of capitate resection allows the use of autograft in a wrist arthrodesis without the additional morbidity of iliac crest bone grafting. This case also demonstrates the importance of appropriate diagnosis and oncologic technique at the index surgery.

476 Background: Lack of standardized reporting and collection of patient-reported outcomes (PROs) limits cross-trial comparisons of first-line IO-based regimens for mRCC. Prospectively collected real world data may fill this important knowledge gap. Pts with stable/improved QoL at 3 mo versus baseline have longer median OS than pts with worse/unobserved HRQoL versus baseline (Cella, 2024). Methods: ODYSSEY is a multi-site, prospective observational study of 468 US pts with mRCC. Pts must have mRCC (any histology), no prior systemic therapy (ST), and follow up at a PCORnet study site. Exclusion criteria include treatment for cancer except mRCC. Descriptive statistics are used to show PRO score changes from baseline. We evaluate longitudinal change from baseline in PRO scores using least squares mean (LSM). Minimally important differences (MID) are 3 points for FKSI-19 total score, 1 point for the FKSI-Disease Related Symptoms (DRS) subscale and 7 points for FACT-G. Higher score indicates better QOL. The primary objective is to determine patterns of change in QOL and symptom burden of pts with mRCC. Results: As of 10/1/25, 360 pts were managed with ST, including 266 pts on IO-based combinations: 35 cabozantinib + nivolumab (C+N), 49 lenvatinib + pembrolizumab (L+P), 40 axitinib + pembrolizumab (A+P), and 142 ipilimumab + nivolumab (I+N). Overall median follow-up is 12.1 mos (IQR 6, 24). Age, sex and race were similar across regimens. Prior nephrectomy (50%) was lower than in trials. C+N and L+P pts had less clear cell (56 and 65%) versus A+P and I+N pts (94 and 82%). A+P pts had more favorable IMDC risk (19%) and less poor risk (14%). Baseline QOL was variable across regimens, with L+P generally the lowest. Absolute changes in PROs from enrollment to mo 3 (early change) by regimen are shown in the Table. LSM change from baseline in FKSI-19 and FKSI-DRS favored IO-IO versus IO-TKI at 3 mos but not at 6 mos (not shown). Conclusions: While early change in PROs did not meet the MID threshold between the IO-TKI and I+N cohorts, different patterns of early change are apparent among specific IO-TKI regimens. IO-TKI regimens exhibited higher variation in early PRO change vs I+N. As the data matures, we will associate baseline PROs and early PRO changes with early death and other outcomes. Clinical trial information: NCT04919122 . 3 month change. Instrument C+N (N=35) L+P (N=49) A+P (N=40) All IO-TKI(N=124) I+N(N=142) FKSI-19, N (%) 26 (74) 33 (67) 33 (83) 92 (74) 104 (73) Mean (SD) -0.3 (11) 2.8 (13) -3.2 (12) -0.2 (12) 0.7 (10) Median (IQR) 1.4 (-7, 6) 5.0 (-7, 11) -1.0 (-14, 5) 1.4 (-10, 8) -0.3 (-5, 6) FKSI-DRS, N (%) 26 (74) 33 (67) 33 (83) 92 (74) 104 (73) Mean (SD) -0.8 (5) 1.5 (7) -1.8 (6) -0.3 (6) 0.8 (5) Median (IQR) -0.5 (-5, 3) 2.0 (-5, 5) -1.0 (-5, 3) 0.0 (-5, 4) 0.0 (-2, 4) FACT-G, N (%) 27 (77) 32 (65) 29 (73) 88 (71) 102 (72) Mean (SD) 2.1 (14) 5.2 (16) -3.5 (15) 1.4 (15) 0.3 (13) Median (IQR) 4.0 (-4, 10) 1.2 (-6, 13) -6.4 (-11, 4) 1.6 (-8, 10) 1.6 (-7, 8)