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Objective To provide a comprehensive analysis of initial suicide attempts, covering incidence, risk factors, outcomes, and healthcare use in the month before and the month after the attempts. Design Comprehensive analysis of the Swedish population that included three designs: a retrospective cohort study to investigate incidence and healthcare use, a nested case-control study to investigate risk factors, and a matched cohort study to examine subsequent suicide attempts and mortality. Setting Comprehensive Swedish national registers that include patient diagnoses from hospitals and specialist outpatient care, and cause of death information updated to the end of 2019. Participants 3.7 million people born in Sweden in 1963-98 and followed from age 10 to 57 years. Main outcome measure First lifetime suicide attempt identified in patient and death registers using ICD (international classification of diseases) codes for intentional self-harm, any self-harm with lethal methods or requiring hospital admission, or any self-harm resulting in death. Results The lifetime risk of an initial suicide attempt in the study population was 4.6%, with greater risk in females and highest risk between ages 18 and 24. One in 10 families in Sweden had at least one family member who attempted suicide. Overdose and poisoning were the most common methods. Previous psychiatric disorders, general medical diseases, and adverse life events were associated with increased risk of initial suicide attempt, while higher socioeconomic status was associated with decreased risk. People with an initial suicide attempt were at substantially increased risk of subsequent attempts (hazard ratio 23.4), death by suicide (16.4), and all cause mortality (7.3). At least 60% of those who made an initial suicide attempt had a healthcare contact in the month before the attempt. Conclusions This study provides comprehensive data on the incidence, risk factors, outcomes, and healthcare use of initial suicide attempts in the Swedish population, highlighting the need for systematic prevention efforts for people who have attempted suicide for the first time.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Background Disability disclosure and accommodation requests among US medical students have increased significantly, yet gaps in support persist. Disability resource professionals (DRPs) are one essential support in bridging these gaps, but only 9% of medical schools employ a dedicated DRP, leaving institutions potentially underprepared to address the needs of students with disabilities. Objective This study explored the roles, qualifications, and challenges of DRPs in US medical schools to identify barriers to job performance and inform strategies for strengthening and supporting this role in medical education. Methods An exploratory, cross-sectional survey was conducted in July to August 2023. A 27-question online survey was distributed through convenience and snowball strategy via social media and listservs. Questions addressed institutional structures, the size of DRP student caseloads, job satisfaction, mentorship, and barriers to managing caseloads. Quantitative data were analyzed using descriptive statistics and χ 2 tests, qualitative responses were thematically analyzed. The University of Michigan IRB approved this study. Results Seventy-nine DRPs from 72 US MD and 7 DO programs participated. Most respondents reported excessive workloads, with 30% managing caseloads exceeding 100 students. Less than half of DRPs (45.6%) indicated that their workload was manageable. Inadequate professional development, lack of mentorship, and low salary satisfaction emerged as common challenges. Respondents also reported institutional barriers, including stigma, faculty resistance to accommodations, and the complexity of coordinating disability accommodations across didactic, clinical, and testing environments. Discussion DRPs are critical to fostering accessible and inclusive medical education, yet systemic barriers undermine their effectiveness and place institutions at risk of increased student attrition, legal liability, and resource strain. Addressing these challenges requires investments in manageable caseloads, professional development for DRPs, faculty training, and institutional prioritization of the DRP role. Conclusions Systemic investments in staffing, training, and institutional culture are necessary to support DRPs and the growing population of US medical students with disabilities (MSWDs).

BACKGROUND AND OBJECTIVES: Aneurysm risk prediction remains an imprecise science that places patients at risk for either over or undertreatment. Machine learning (ML) models may improve clinical practice by adding precision to risk assessment. This study aims to comprehensively assess the current landscape of ML applications in predicting the risk of aneurysm rupture and compare the performance with the widely used PHASES score. METHODS: A systematic review of PubMed, Scopus, and Web of Science was conducted. All studies using ML tools to predict the rupture risk of intracranial aneurysms were included. Meta-analysis was conducted with consideration to the ML algorithms and compared with the PHASES score. RESULTS: Thirty-six studies involving 22 462 patients were included in the final analysis. ML techniques, including 124 models using 25 algorithms, were employed. Among various ML models, while they had comparable diagnostic performance, deep learning exhibited a slightly better performance profile (sensitivity = 0.792, specificity = 0.788, and accuracy = 0.778 in external validation). Based on our analysis, ML, regardless of the algorithm, provides comparable sensitivity (0.743 vs 0.771, P = .60) and higher specificity (0.763 vs 0.507, P < .01) compared with the PHASES score. Consistently, pooling the area under the receiver operating characteristic curve (AUC) for 60 ML models and 5 PHASES score data, ML models exhibited higher AUC (0.84 vs 0.64, P < .01). Using hemodynamic parameters as input for models improved specificity ( P < .01) in the test sets without any significant changes in the sensitivity. The later improvement was not observed in the external validation sets. CONCLUSION: ML techniques have the potential to enhance the prediction of intracranial aneurysm rupture compared with traditional approaches, like the PHASES score. Incorporating hemodynamic parameters may further enhance the accuracy of ML models. Feature prospective studies are required to validate the utility of ML models for clinical integration.

Objective: This study aimed to evaluate the characteristics, clinical outcomes, and resource use of patients with unresectable hepatocellular carcinoma (uHCC) treated with first-line (1L) atezolizumab plus bevacizumab (A+B) at five United States (US) institutions: the Mayo Clinic, Houston Methodist, Moffitt Cancer Center, Mays Cancer Center, and University of Arizona. Methods: Treating oncologists extracted data from medical charts of patients with uHCC who were treated with A+B after 1 January 2019. Real-world progression-free survival (rwPFS) and overall survival (OS) were assessed using the Kaplan–Meier method for the overall cohort and for a “trial-like” subgroup with characteristics similar to those in the IMbrave150 trial (Eastern Cooperative Oncology Group Performance Status [ECOG PS] 0–1, Child–Pugh [CP] class A, albumin–bilirubin grade 1–2). Results: Of the 300 patients in the overall cohort (median age of 68 years; 12% ECOG PS ≥ 2; 73% CP A; 26% CP B; median follow-up of 8.7 months), the median rwPFS was 6.8 (95% confidence interval [CI]: 5.8, 8.4) months, and the median OS was 14.4 (95% CI: 12.3, 18.2) months. In the trial-like subgroup (n = 194), the median rwPFS was 8.8 (95% CI: 7.6, 12.1) months and the median OS was 19.5 (95% CI: 14.6, 24.7) months. A significantly lower proportion of patients with CP A compared with CP B (39.7% vs. 73.4%) experienced hospitalization within one year of A+B initiation, whereas hospitalizations due to treatment-related adverse events were similar. Conclusions: This study provides insights into the real-world effectiveness of 1L A+B in a diverse US patient cohort, with results from trial-like patients supporting the reproducible efficacy of A+B in clinical practice.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P =0.02; I 2 =0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P =0.03, I 2 =0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

e17035 Background: 177 Lu-PSMA-617 was approved in March 2022 for patients with mCRPC pretreated with an androgen receptor pathway inhibitor (ARPI) and a taxane. There are limited data on the effectiveness of treatments post- 177 Lu-PSMA-617. The aim of this study was to describe prostate-specific antigen (PSA) responses among patients with mCRPC receiving a guideline-recommended therapy as the next therapy after 177 Lu-PSMA-617 treatment. Methods: This retrospective, observational study used real-world data from the PRECISION data platform, a proprietary dataset developed by Novartis, comprised of patient-level electronic health record and claims data that represent the US advanced prostate cancer population in the community, academic, urology, and medical oncology settings. Patients with mCRPC who received any guideline-recommended therapy at least 14 days after treatment with 177 Lu-PSMA-617 between March 23, 2022 and July 31, 2024 were included. Guideline-recommended therapies included abiraterone, enzalutamide, darolutamide, apalutamide, cabazitaxel, docetaxel, pembrolizumab, sipuleucel-T, niraparib, olaparib, talazoparib, rucaparib, and radium-223. Patients’ PSA values while on 177 Lu-PSMA-617 treatment were compared with their PSA values during the subsequent therapy course. Proportions of patients achieving reductions in PSA levels ≥50% (PSA50) and ≥80% (PSA80) were estimated. All analyses were descriptive. Results: A total of 152 patients receiving any subsequent guideline-recommended therapy after 177 Lu-PSMA-617 were identified. Mean age was 72.1 years. Most patients received an ARPI (n=93, 61.2%) – abiraterone (n=38), enzalutamide (n=37), darolutamide (n=10), or apalutamide (n=8) – as their subsequent therapy. Of patients who received a taxane (n=42, 27.6%), 24 received cabazitaxel and 18 received docetaxel. Median time to initiation of subsequent therapy was 206 days (interquartile range [IQR] 101–301 days) from 177 Lu-PSMA-617 initiation and 44 days (IQR 17–119 days) from 177 Lu-PSMA-617 discontinuation. Overall, among patients with sufficient information for PSA evaluation (n=30), 46.7% achieved PSA50 and 40.0% PSA80 post- 177 Lu-PSMA-617. Among patients receiving an ARPI, PSA50 was observed in 11/18 (61.1%) and PSA80 in 10/18 (55.6%). Among patients receiving a taxane, PSA50 and PSA80 were seen in 3/12 (25.0%) and 2/12 (16.7%), respectively. Conclusions: In this real-world analysis, the majority of patients who received guideline-recommended therapies after 177 Lu-PSMA-617 achieved at least a PSA50 response, suggesting that 177 Lu-PSMA-617 treatment does not preclude response to other subsequent therapies.

e17030 Background: The broad therapeutic arsenal for mCRPC, with overlapping indications, makes selecting the optimal treatment sequence challenging in clinical practice. The aim of this study was to evaluate the prostate-specific antigen (PSA) responses and overall survival (OS) among patients with mCRPC receiving 177 Lu-PSMA-617 based on prior ARPI and taxane treatment exposure. Methods: This retrospective, observational study used real-world data from the PRECISION data platform, a harmonized dataset of advanced prostate cancer patients in the US from diverse clinical settings. Patients with mCRPC who had received ≥1 dose of 177 Lu-PSMA-617 between March 23, 2022 and July 31, 2024, after prior treatment with ≥1 ARPI and ≥1 taxane, were included. To assess PSA response, the baseline PSA value obtained within 90 days before starting 177 Lu-PSMA-617 was compared with the on-treatment PSA value obtained ≥28 days after 177 Lu-PSMA-617 initiation. The number of patients achieving PSA reductions ≥50% (PSA50) and ≥80% (PSA80) were estimated, with patients classified into two cohorts based on prior ARPI and taxane exposure: (1) prompt cohort: after only 1 ARPI and 1 taxane, and (2) deferred cohort: >1 ARPI and/or >1 taxane. Patient characteristics and treatment patterns were evaluated descriptively. OS from 177 Lu-PSMA-617 initiation was estimated using Kaplan–Meier methodology. Results: A total of 431 patients were included: 177 patients in the prompt cohort and 254 patients in the deferred cohort. Of patients in the deferred cohort, 185 (72.8%) received ≥1 ARPI and 1 taxane, 32 (12.6%) received 1 ARPI and ≥1 taxane, and 37 (14.6%) received ≥1 ARPI and ≥1 taxane. Median (interquartile range) age was 73 (67–78) years and most demographic characteristics were balanced between groups. Patients in the deferred cohort had higher median PSA levels at baseline (63.1 ng/mL vs 25.2 ng/mL). PSA50 was observed in 18/33 (55%) patients in the prompt cohort vs 28/66 (42%) in the deferred cohort. PSA80 was observed in 13/33 (39%) patients in the prompt cohort vs 21/66 (31%) in the deferred cohort. Across both cohorts, median OS was 18.0 months (95% confidence interval [CI]: 15.1 months–not reached [NR]). Median OS was NR in patients in the prompt cohort vs 15.1 months in patients in the deferred cohort (95% CI: 11.6 months–NR). Conclusions: In this large real-world study, prompt initiation of 177 Lu-PSMA-617 (after only 1 ARPI and 1 taxane) showed superior clinical outcomes versus deferred initiation of 177 Lu-PSMA-617. Patients were more likely to achieve a PSA reduction ≥50% and ≥80% and had longer OS with prompt initiation of 177 Lu-PSMA-617. These results may help to guide treatment sequencing in clinical practice.

TPS5127 Background: Androgen deprivation therapy (ADT) ± androgen receptor pathway inhibitor therapy is a primary treatment for metastatic hormone-sensitive prostate cancer, but is noncurative and has significant toxicities when used long-term. In patients with OMPC for whom delaying ADT is appropriate, metastasis-directed therapy such as stereotactic body radiation therapy (SBRT) has been shown to provide local disease control. However, many patients do not experience a complete prostate-specific antigen (PSA) response and develop poly-metastatic disease. [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) is a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with demonstrated efficacy and a manageable safety profile in patients with PSMA-positive metastatic castration-resistant prostate cancer in the VISION and PSMAfore trials. PSMA-DC (NCT05939414) is an ongoing, international, randomized phase 3 trial to evaluate the efficacy of 177 Lu-PSMA-617 versus observation after SBRT in delaying castration and disease progression in patients with PSMA-positive OMPC. Methods: Eligible patients have histologically confirmed prostate cancer, biochemical recurrence post-definitive treatment, OMPC with ≤ 5 PSMA-positive metastatic lesions including ≥ 1 distant metastasis on PSMA PET/CT scans (all must be amenable to SBRT), PSA doubling time < 10 months and non-castration testosterone levels (> 100 ng/dL). Exclusion criteria include distant metastasis by conventional imaging (CI; CT/MRI and bone scans) at screening, prior ADT (except adjuvant ADT completed > 12 months before randomization), or other systemic therapy for metastatic prostate cancer. Patients (N = ~450) will be randomized 2:1 to 177 Lu-PSMA-617 or observation and will receive SBRT to all metastatic lesions within 14 days, completed within 3 weeks. Patients will then receive either intravenous 177 Lu-PSMA-617 (7.4 GBq/6 weeks; 4 cycles), starting 7–21 days after SBRT, or undergo observation only. Additional SBRT for new lesions is allowed. ADT is allowed after a metastasis-free survival (MFS) event by CI confirmed by blinded independent review committee (BIRC). Safety follow-up will occur 42 days after the last 177 Lu-PSMA-617 dose and at the week 24 visit for the observational arm. Long-term follow-up for the 177 Lu-PSMA-617 arm will include safety assessments every ~32 weeks. The primary endpoint is MFS by CI as assessed by BIRC using RECIST v1.1, or death. To provide 90% power to detect a hazard ratio of 0.6, 187 MFS events are required. The key secondary endpoint is time to next hormonal therapy. Additional secondary endpoints include time to PSA progression, radiographic progression-free survival, symptomatic progression, patient-reported health-related quality of life, overall survival and safety. Shore et al. PSMA-delay castration (DC): an open-label, multicenter, randomized phase 3 study of [ 177 Lu]Lu-PSMA-617 versus observation in patients with metachronous PSMA-positive oligometastatic prostate cancer (OMPC). J Urol 2025;213 (5S2_suppl):e28. https://www.auajournals.org/doi/10.1097/01.JU.0001110444.53548.eb . Reused with permission; ©American Urological Association, 2025. This abstract previously presented at 2025 AUA Annual Meeting. Clinical trial information: NCT05939414 .