Citations

Abstract Background While the rate of physician burnout has been characterized as relatively high among urologists compared to other specialties, a specific examination of burnout and predictors of burnout among urologists specializing in sexual medicine has not been conducted. Aim The aim of this study was to collect demographic characteristics of urologists specializing in sexual medicine, assess the occurrence of and risk factors for burnout, and characterize satisfaction with career, compensation and work-life balance. Methods We surveyed 96 urologists specializing in sexual medicine to characterize demographic and practice characteristics and assess their satisfaction with career aspects and levels of burnout. Univariable and multivariable modeling with stepwise variable selection was utilized to identify predictive variables of burnout. Outcomes The Copenhagen Burnout Inventory was used to assess personal burnout, work-related burnout, patient-related burnout, and overall burnout. Results Twenty-four percent (n = 23) of participants reported burnout with 35.4% (n = 34) reporting personal burnout, 38.5% (n = 37) reporting work-related burnout, and 24.0% (n = 23) reporting patient-related burnout. Younger age (P = 0.051), Black/African American or multiracial race compared to white race (P < 0.0001), Latino or Hispanic background (P = 0.034), female sex (P = 0.059), being unmarried (P = 0.047), and increased educational debt (0.030) were identified as predictive of overall burnout in adjusted analysis. Dissatisfaction with work-life balance was significantly related to an increase in all categories of burnout (P < 0.01). Clinical implications These findings may guide practice patterns and initiatives to support groups identified at increased risk of burnout, as well as function as a benchmark for future studies of burnout in the sexual medicine urology community. Strengths and limitations While this is the first study of burnout specifically among sexual medicine urologists and findings are consistent with the overall urology community, the small sample size may lead to a biased sample. Conclusion Several demographic and personal characteristics were identified to be predictive of burnout among the sexual medicine urology community, indicating opportunities for additional support.

ABSTRACT Background Guidelines recommend primary care practitioners (“PCPs”) engage women ≥ 75 years in shared decision‐making (SDM) around mammography screening. Therefore, we aimed to develop a web‐based conversation aid about mammography screening for women ≥ 75 using output from established simulation models to provide screening outcomes based on > 23,000 combinations of individual women's health and breast cancer risk factors. Methods We used an end‐user centered design approach to develop a prototype web‐based conversation aid incorporating feedback. From July 2023 to April 2024, 10 PCPs from a Boston‐area health system and a safety‐net hospital used the prototype aid during encounters with women ≥ 75 without breast cancer or dementia ( n = 30; 1–5 patients per PCP). We observed aid use and assessed clinician effort to involve patients in SDM using OPTION5 (assesses five components of SDM, scores range 0–100). We surveyed PCPs and patients about the aid's acceptability. Patients completed the SDM‐process scale (scores range 0–4) to rate the SDM quality experienced. Participants' comments were subject to thematic analysis. Results Of 10 PCP ‐participants, seven were female and four were community‐based. Of 30 patient‐participants, 22 (73%) were non‐Hispanic White, 9 (30%) had ≥ 2 Charlson comorbidities and mean age was 78.5 years ( SD 2.8). Nine PCPs agreed that the aid helped them with SDM and was easy‐to‐use; six felt it had too much information; and seven planned to continue using the aid. Patients rated the SDM ‐process highly (scores = 3.0 [ SD 0.9]) and we observed high SDM (mean OPTION5 = 77.9 [ SD 20.6]). Participants felt the aid was “empowering” and “helpful for decision‐making.” After SDM discussions, seven patients intended to stop screening, nine to screen less frequently, and 14 to continue screening regularly. Conclusions We developed a novel conversation aid that supports SDM about mammography screening with women ≥ 75 years. Lessons learned will guide revisions of a final tool for testing in a clinical trial.

ABSTRACTObjectiveWhile endoscopic laser wedge excision (LWE) for iSGS demonstrated lower surgical recurrence rates compared to endoscopic dilation (ED), ED remains the primary technique employed. Additionally, serial intralesional steroid injections (SILSIs) also demonstrate benefits in controlling disease. We aimed to compare surgical recurrence rates following ED, ED + SILSI, and LWE following a patient's first operation.MethodsThis was a two‐center retrospective analysis of iSGS patients who underwent either ED, ED + SILSI, or LWE. Patients were followed to their last follow‐up date or reoperation. Kaplan–Meier analysis and Cox proportional hazards were used to evaluate the recurrence times across the different surgical groups with additional stratification by age, compliance to medical adjuvant therapy, and percentage of stenosis rated at reoperation.ResultsA total of 126 patients from Institution 1 underwent LWE, while at Institution 2, ED and ED + SILSI were performed on 32 and 23 patients, respectively. One‐year recurrence estimates were 9%, 53%, and 0% for LWE, ED, and ED + SILSI, respectively, while 5‐year recurrence estimates were 45%, 90%, and 19%, respectively. Adjusted Cox‐proportional hazard ratios demonstrated a greater risk of surgical recurrence with ED compared to LWE (2.25; 95% confidence interval [CI]: 1.31–3.88) and no difference between ED + SILSI and LWE (0.84; 95% CI: 0.32–2.25).ConclusionLWE demonstrates reduced recurrence times compared to ED when controlling for surgery number, age, triple therapy compliance, and percentage of stenosis at reoperation. The application of postoperative SILSI appears to similarly reduce recurrence rates comparable to LWE and warrants further investigation.

Abstract Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2025 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2025 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, specialty drugs and vaccines. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2024 were made based on a combination of quantitative analyses and expert opinion. Results In 2024, overall pharmaceutical expenditures in the US grew 10.2% compared to 2023, for a total of $805.9 billion. Utilization (a 7.9% increase) and new drugs (a 2.5% increase) drove this increase, while prices remained flat (a 0.2% decrease). Semaglutide was the top drug in 2024, followed by tirzepatide and adalimumab. Drug expenditures were $39.0 billion (a 4.9% increase) and $158.2 billion (a 14.4% increase) in nonfederal hospitals and clinics, respectively. In clinics, increased utilization drove growth, with a small contribution from new products, while prices remained flat. In nonfederal hospitals, new products, price, and new volume each contributed modestly to growth in spend. Several new drugs that will influence spending are expected to be approved in 2025. Specialty, endocrine, and cancer drugs will continue to drive expenditures. Conclusion For 2025, we expect overall prescription drug spending to rise by 9.0 to 11.0%, whereas in clinics and hospitals we anticipate an 11.0% to 13.0% increase and a 2.0% to 4.0% increase, respectively, compared to 2024. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending.

Abstract Background The ataxia-telangiectasia mutated (ATM) protein coordinates the cellular response to therapeutic radiation, and ATM inhibitors can potentially enhance the efficacy of radiation in otherwise radiation-resistant tumors. Methods The small molecule ATM kinase inhibitor WSD0628 was specifically designed for enhanced distribution across the blood-brain barrier to more effectively treat glioblastoma (GBM) and brain metastases in combination with radiation therapy (RT). GBM and brain metastasis patient-derived xenograft models were used to understand target inhibition, radiosensitization, inhibition of the DNA damage response, and in vivo efficacy. Results Initial in vitro characterization of WSD0628 demonstrates a high level of selectivity across kinase families, limited aldehyde oxidase liability, and low risk of hERG interactions. Consistent with a central role for ATM in radiation response, WSD0628 blocked radiation-induced signaling and enhanced radiosensitivity in U251 glioma cells and brain tumor PDXs GBM120 and M12. In comparison to control or RT alone in orthotopic PDXs, the combination of WSD0628 with RT markedly prolonged median survival—GBM12 (19, 55, and 408 days, respectively); GBM43 (26, 44, and 143 days, respectively); GBM120 (51, 89, and 231 days, respectively); M12 (17, 39, and 190 days, respectively). Pharmacokinetic and pharmacodynamic testing after treatment in orthotopic GBM43 tumors showed inhibitory levels of WSD0628 and a reduction of γH2AX foci in the combination-treated tumors. Conclusions Collectively, these results suggest a promising role for WSD0628 in combination with RT in brain tumors and provide the rationale for an ongoing Phase 0/1A clinical trial testing this combination in recurrent GBM.

Background: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are leading causes of transfusion-related morbidity and mortality. Soluble factors in erythrocyte supernatant may increase risk for these complications. The authors hypothesized that point-of-care allogeneic erythrocyte washing may be an effective intervention to mitigate elevations in soluble factors as well as physiologic responses associated with transfusion-associated respiratory complications in the setting of cardiac surgery. Methods: This is a two-center, nonblinded, randomized clinical trial evaluating point-of-care washed versus standard issue allogeneic erythrocyte transfusions administered during or on the day of cardiac surgery. The primary analysis was performed via modified intention to treat. The primary outcomes assessed were changes in intermediate markers of lung injury as well as cardiopulmonary physiologic responses to erythrocyte transfusion. Secondary outcomes included the duration of intensive care unit and hospital stay, durations of mechanical ventilation and oxygen supplementation, presence of TRALI or TACO, and mortality. Results: Among 154 analyzed patients (81 washed, 73 standard issue), the median age was 66 yr, and 77 (50.0%) were women. The median (interquartile range) number of allogeneic erythrocyte units transfused on the day of surgery was 3.0 (2.0 to 5.0) in the washed erythrocyte group and 3.0 (2.0 to 4.0) in the standard issue group (P = 0.13). No between-group differences were identified in any of the assessed recipient lung injury biomarkers (all P values > adjusted alpha). Durations of intensive care unit stay (median [interquartile range], 3.0 [2.0 to 5.0] vs. 3.0 [2.0 to 4.0] days; P = 0.117) and hospital length of stay (12.0 [9.0 to 17.0] vs. 12.0 [9.0 to 17.0] days; P = 0.801) were similar, as were the number of ventilator-free days at day 28 (27.0 [27.0 to 27.0] vs. 27.0 [26.0 to 27.0]; P = 0.699) and oxygen-free days at day 28 (24.0 [19.0 to 26.0] vs. 24.0 [22.0 to 26.0]; P = 0.400). No significant differences were noted in mortality rate or in incidence rates for TRALI, TACO, and acute kidney injury. Conclusions: Among patients undergoing cardiovascular surgery with high risk of erythrocyte transfusion, point-of-care washing of allogeneic erythrocyte transfusions did not mitigate changes in intermediate markers of lung injury or cardiopulmonary physiologic responses to erythrocyte transfusion and was not associated with improved clinical outcomes.

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and the activated B cell–like subtype (ABC-DLBCL) is associated with particularly poor outcome. Many ABC-DLBCLs harbor gain-of-function mutations that cause inappropriate assembly of the CARMA1-BCL10-MALT1 (CBM) signalosome, a cytoplasmic complex that drives downstream NF-κB signaling. MALT1 is the effector protein of the CBM signalosome such that its recruitment to the signalosome via interaction with BCL10 allows it to exert both protease and scaffolding activities that together synergize in driving NF-κB. Here, we demonstrate that a molecular groove located between two adjacent immunoglobulin-like domains within MALT1 represents a binding pocket for BCL10. Leveraging this discovery, we performed an in silico screen to identify small molecules that dock within this MALT1 groove and act as BCL10-MALT1 protein-protein interaction (PPI) inhibitors. We report the identification of M1i-124 as a first-in-class compound that blocks BCL10-MALT1 interaction, abrogates MALT1 scaffolding and protease activities, promotes degradation of BCL10 and MALT1 proteins, and specifically targets ABC-DLBCLs characterized by dysregulated MALT1. Our findings demonstrate that small-molecule inhibitors of BCL10-MALT1 interaction can function as potent agents to block MALT1 signaling in selected lymphomas, and provide a road map for clinical development of a new class of precision-medicine therapeutics.

Background: Cervical cancer screening with a self-collected vaginal specimen for human papillomavirus (HPV) testing was approved by the U.S. Food and Drug Administration in May 2024, offering a potential solution to declining screening rates. Objective: We aimed to assess acceptability of clinic-based vaginal specimen self-collection for HPV testing and to evaluate associations between participants’ sociodemographics and their likelihood of choosing self-collection for future screening and the overall acceptability of using the Evalyn® brush device. We also evaluated associations between specific acceptability constructs and reported likelihood to use the device in the future and overall acceptability. Methods: Following self-collection of a vaginal specimen, participants completed an electronic survey that measured constructs from the Theoretical Framework of Acceptability. Associations were assessed using logistic regressions. The study was conducted at a colposcopy clinic in the Gynecology department of a midwestern academic medical center in the United States from November 2022 through July 2023. Results: Participants ( n = 81) reported high likelihood (98% likely or very likely) of choosing in-home self-collection for future screening and unanimity on overall acceptability (100% acceptable or completely acceptable) of using the device. More affirmative responses to measures on instruction understandability, ease of device use, understanding the device is used for cervical cancer screening, and perceiving self-collection improves screening rates were associated with a higher likelihood to choose self-collection for future screenings and overall acceptability of the device (all p values <0.05). Conclusion: Vaginal specimen self-collection for HPV testing was well-received in the studied population, with high acceptability and likelihood of uptake. Implementation efforts should provide user-friendly instructions and emphasize the benefits of self-collection for cervical cancer screening, particularly among people less likely to engage with clinician-collected speculum-based screening.