Schmidt, Walker M.

Abstract Background Congenital hemophilias affect about 30,000 US individuals (0.01% of the population) and atrial fibrillation (AF) about 10.5 million US individuals (4.5% of the population). Stroke prevention in this population is limited to expert opinion with formal guideline development hindered by a lack of clinical trials. Herein, we correlate outcomes of major bleeding and ischemic stroke with CV risk factors and antithrombotic management in our patient cohort. Methods This is a retrospective review (minimal risk study) of patients with hemophilia A, B, or C and concomitant AF diagnosed between 2000 and 2025. Patients were identified through a Mayo Clinic Rochester database using key terms. All cases were manually reviewed in the electronic medical record for appropriateness. Major bleeding was defined per International Society on Thrombosis and Haemostasis (ISTH) criteria. Stroke and bleeding risk were based on CHA₂DS₂-VASc and HAS-BLED scores. Analyses were performed using BlueSky Statistics software, with chi-square tests for categorical variables and Mann-Whitney U tests for continuous variables. Results A total of 21 patients were identified. Of these, 18 (86%) were male. Common comorbidities included type 2 diabetes (T2DM) in 14 (67%), hyperlipidemia in 18 (86%), hypertension in 18 (86%), and coronary artery disease in 12 (57%). Fifteen (71%) were never smokers. One patient (5%) had HIV on antiretroviral therapy, and five (24%) had a history of localized, resected cancer. Congenital hemophilia A was present in 12 patients (57%), hemophilia B in 5 (24%), and hemophilia C in 5 (24%). The median age at hemophilia diagnosis was 55.3 years. Hemophilia severity was mild in 17 (81%) and moderate in 4 (19%). Median factor level was 33% (SD=12.77%). Most were diagnosed with hemophilia from accumulation of minor bleeding events and family history. Six (29%) had major bleeds prior to AF diagnosis. The median age at AF diagnosis was 65.6 years. Paroxysmal AF was the most common subtype (11 patients; 52%), followed by permanent (5; 24%) and persistent (5; 24%). Median CHA₂DS₂-VASc and HAS-BLED scores at AF diagnosis were 2 and 1, respectively. At AF diagnosis, 2 patients (10%) were already on antithrombotic therapy (aspirin 81 mg [ASA]), both for recent transcatheter aortic valve replacement (TAVR). For AF-related stroke prevention, 5 patients (24%) were started on ASA and 5 others (24%) were started on apixaban. Cardioversion was performed in 5 patients (24%) and ablation in 2 (10%)). Five (24%) underwent procedural interventions (3 Watchman devices, 2 Maze procedures). Three patients (14%) had at least one major bleed following AF diagnosis. Bleed locations included traumatic intracranial, severe epistaxis, and spontaneous intracranial (one each). At the time of bleed, one patient was on ASA and two were on no antithrombotic or anticoagulation. One patient (5%) had a second major bleed – a muscle hematoma. He was not on antithrombotic or anticoagulation at the time. Two bleeds were fatal. Patient 1 was an 83-year-old male with moderate hemophilia A, a history of major GI bleed prior to AF diagnosis, a CHA₂DS₂-VASc score of 7 on ASA (taken for 11.5 years), and a HAS-BLED score of 3 who died of complications from severe epistaxis.Patient 2 was a 56-year-old male with moderate hemophilia B, a CHA₂DS₂-VASc score of 1, and a HAS-BLED score of 1 that died from a spontaneous intracranial bleed. One patient experienced an ischemic stroke: a 71 year old male with moderate Hemophilia A, a CHA₂DS₂-VASc score of 7, and a HAS-BLED score of 5 who was anticoagulated on apixaban. Conclusion: Despite the relatively low use of anticoagulation and antithrombotic, nearly 15% of this cohort experienced major bleeding after AF diagnosis, including two fatal events. Ischemic stroke was rare but occurred in a high-risk patient that was anticoagulated with apixaban. These findings demonstrate limitations of existing risk-stratification tools in this unique population, and support the need for larger studies and evidence based guidelines for patients with bleeding disorders and AF.

Abstract Background Female underrepresentation in oncology clinical trials can result in outcome disparities. We evaluated female participant representation in US oncology trials by intervention type, cancer site, and funding. Materials and Methods Data were extracted from the publicly available Aggregate Analysis of ClinicalTrials.gov database. Initially, 270,172 studies were identified. Following the exclusion of trials using Medical Subject Heading terms, manual review, those with incomplete status, non-US location, sex-specific organ cancers, or lacking participant sex data, 1650 trials consisting of 240,776 participants remained. The primary outcome was participation to prevalence ratio (PPR): percent females among trial participants divided by percent females in the disease population per US Surveillance, Epidemiology, and End Results Program data. PPRs of 0.8-1.2 reflect proportional female representation. Results Females represented 46.9% of participants (95% CI, 45.4-48.4); mean PPR for all trials was 0.912. Females were underrepresented in surgical (PPR 0.74) and other invasive (PPR 0.69) oncology trials. Among cancer sites, females were underrepresented in bladder (odds ratio [OR] 0.48, 95% CI 0.26-0.91, P = .02), head/neck (OR 0.44, 95% CI 0.29-0.68, P < .01), stomach (OR 0.40, 95% CI 0.23-0.70, P < .01), and esophageal (OR 0.40 95% CI 0.22-0.74, P < .01) trials. Hematologic (OR 1.78, 95% CI 1.09-1.82, P < .01) and pancreatic (OR 2.18, 95% CI 1.46-3.26, P < .01) trials had higher odds of proportional female representation. Industry-funded trials had greater odds of proportional female representation (OR 1.41, 95% CI 1.09-1.82, P = .01) than US government and academic-funded trials. Conclusions Stakeholders should look to hematologic, pancreatic, and industry-funded cancer trials as exemplars of female participant representation and consider female representation when interpreting trial results.

Abstract Background: Advances in supportive care and novel therapies have driven improved outcomes for patients with Multiple myeloma (MM) and Light Chain Amyloidosis (AL). Unfortunately, this progress demands a heavy toll - higher patient costs. Financial toxicity (FT) is the adverse impact of cancer on a patient's financial well-being, contributing to increased distress, lower medication compliance, and even reduced survival. We aimed to evaluate MM and AL patients for financial toxicity over time to better understand its impact on various quality of life (QOL) domains. Methods: Adult patients with MM or AL that receive care at Mayo Clinic, Rochester MN, were recruited for a prospective study between December 2019 and March 2021. FT was measured using the validated COmprehensive Score for financial Toxicity (COST) questionnaire at the time of enrollment, 3 months, and 6 months follow-up. COST scores range from 0-44, with higher scores indicating lower FT. We defined patients with a COST score of ≤ 23 as having substantial FT. Domains of QOL were assessed via the Patient Reported Outcome Measurement Information System (PROMIS)-29 survey. Patient demographics and clinical information were abstracted from the electronic medical record. Statistical analysis included a comparison of COST scores among groups through Wilcoxon rank-sum, Kruskal-Wallis, and Jonckheere-Terpestra tests for binary, unordered, and ordered categorical variables, respectively. Results: One hundred and sixteen patients (96 MM, 83%; AL 20, 17%) enrolled in this study. The cohort is characterized as follows: 49% age 65+ (51% age 35-64), 54% male, 93% White, 4.3% Black, 3.5% Hispanic, 44% with incomes > USD 75k/yr (26% < USD 50k/yr), 77% with at least some college education (32% graduate or doctoral degree), 52% insured through Medicare (4.3% through Medicaid), 36% employed (53% retired), and 71% married (16% divorced). Forty-three percent of patients enrolled in the study were newly diagnosed (56% relapsed), and 72% had received an autologous stem cell transplant. Baseline mean COST score was25.9 (N=116; SD 10.2), with 37% reporting FT. A total of 101 patients (85 MM; 16 AL) completed a baseline and either 3- or 6-month COST survey. Thirty-eight of these patients (38%) reported FT at the time of enrollment. Among those reporting baseline FT, 71% continued to report FT at 3 or 6 months; 29% showed reduced FT. Of the 62% of patients who reported low FT at baseline, 78% showed continued low FT at 3 or 6 months; 22% showed increased FT. Results of longitudinal follow-up are outlined in Figure 1. FT was significantly associated with increased anxiety, depression, and pain intensity domains on the PROMIS-29. Substantial FT was associated with: women, Medicaid as primary insurance, and being divorced. FT was also greater in unemployed/disabled vs retired individuals. Conversely, low FT was associated with: males, earning > USD 75k/yr, Medicare as primary insurance, having at least some college education, being retired, and traveling 300+ miles for care. Financial toxicity did not differ significantly by age, race, ethnicity, disease status (newly diagnosed vs relapsed), or transplant status. Discussion : Financial toxicity was present in more than one-third of AL and MM patients in this high-earning and well-educated cohort. Financial toxicity was associated with increased anxiety, depression, and pain intensity, contributing to lower patient quality of life. Longitudinal follow-up has shown financial toxicity to be dynamic, necessitating routine evaluation of patient financial burdens. Future work will focus on automating FT assessment with incorporation into routine care and developing care processes to support patients. Figure 1 Figure 1. Disclosures Dispenzieri: Alnylam: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Oncopeptides: Consultancy; Sorrento Therapeutics: Consultancy; Janssen: Consultancy, Research Funding.