Citations

BACKGROUND: A gender-based compensation gap among physicians is well documented. Even after adjusting for age, experience, work hours, productivity, and academic rank, the gender gap remained and widened over the course of a physician’s career. This study aimed to examine if a significant gender pay gap still existed for anesthesiologists in the United States. METHODS: In 2018, we surveyed 28,812 physician members of the American Society of Anesthesiologists to assess the association of compensation with gender and to identify possible causes of wage disparities. Gender was the primary variable examined in the model, and compensation by gender was the primary outcome. Compensation was defined as the amount reported as direct compensation on a W-2, 1099, or K-1, plus all voluntary salary reductions (eg, 401[k], health insurance). The survey directed respondents to include salary, bonuses, incentive payments, research stipends, honoraria, and distribution of profits to employees. Respondents had the option of providing a point estimate of their compensation or selecting a range in $50,000 increments. Potential confounding variables that could affect compensation were identified based on a scoping literature review and the consensus expertise of the authors. We fitted a generalized ordinal logistic regression with 7 ranges of compensation. For the sensitivity analyses, we used linear regressions of log-transformed compensation based on respondent point estimates and imputed values. RESULTS: The final analytic sample consisted of 2081 observations (response rate, 7.2%). This sample represented a higher percentage of women and younger physicians compared to the demographic makeup of anesthesiologists in the United States. The adjusted odds ratio associated with gender equal to woman was an estimated 0.44 (95% confidence interval, 0.37–0.53), indicating that for a given compensation range, women had a 56% lower odds than men of being in a higher compensation range. Sensitivity analyses found the relative percentage difference in compensation for women compared to men ranged from −8.3 to −8.9. In the sensitivity analysis based on the subset of respondents (n = 1036) who provided a point estimate of compensation, the relative percentage difference (−8.3%; 95% confidence interval, −4.7 to −11.7) reflected a $32,617 lower compensation for women than men, holding other covariates at their means. CONCLUSIONS: Compensation for anesthesiologists showed a significant pay gap that was associated with gender even after adjusting for potential confounding factors, including age, hours worked, geographic practice region, practice type, position, and job selection criteria.

Abstract Respiratory tract infections (RTIs) drive many outpatient encounters and, despite being predominantly viral, are associated with high rates of antibiotic prescriptions. With rising antibacterial resistance, optimization of prescribing of antibiotics in outpatients with RTIs is a critical need. Fortunately, this challenge arises at a time of increasing availability of novel RTI diagnostics to help discern which patients have bacterial infections warranting treatment. Effective implementation of antibiotic stewardship is needed, but optimal approaches for ambulatory settings are unknown. Future research needs are reviewed in this summary of a research summit convened by the Infectious Diseases Society of America in the fall of 2019.

Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association. We identified 7 patients who had shunts and subsequently developed mesothelioma (5 women; median age: 31 y, range: 18 to 45 y). Clinical history and pathology materials were reviewed, and RNA sequencing was performed. Clinical presentations varied; 6 patients had hydrocephalus and a ventriculoperitoneal shunt, and 1 patient had portal hypertension and a portoatrial shunt. The median duration of shunt therapy in 5 cases was 29 years (range: 12 to 35 y); the remaining 2 patients also had shunts for many years, but specific details were unavailable. Two patients had radiotherapy for malignancies in childhood. One had an alleged exposure to asbestos and 1 had prior exposure to talc. The rest had no known risk factors. Histologically, all tumors were purely epithelioid. Treatments included surgical debulking, chemotherapy, and palliative care. All 7 died of disease (median survival: 7 mo, range: 1 to 18 mo). Molecular testing showed loss of NF2 and CDKN2A/B and a BAP1 mutation in 1 case, and no genomic alterations associated with mesothelioma in 2 cases. Peritoneal mesothelioma may represent a complication of long-standing indwelling shunt catheters. The mechanism is unknown, but chronic peritoneal irritation may play a role. Albeit rare, mesothelioma should be considered in patients with a shunt who present with new ascites.

Abstract Abstract 230 The prognosis for patients (pts) with acute myeloid leukemia (AML) who are aged 60 years or older at the time of initial diagnosis is poor. Even for pts achieving a first complete remission (CR1), prospects for long-term survival are poor due to the very high risk of relapse. Conventional myeloablative conditioning followed by allogeneic blood or marrow transplantation is associated with significantly less relapse compared with conventional chemotherapy when performed in younger pts with AML in CR1. However, the toxicity of this approach in older pts is prohibitive. A reduced intensity conditioning (RIC) regimen may mitigate the risk of early toxicity and while early results in older AML pts have been encouraging and suggest disease free survival (DFS) rates above 30% at 3 yrs (Farag et al, Biol Blood Marrow Transplant 2011), most data are retrospective and pts have not been treated uniformly. We therefore sought to determine the effectiveness of a uniform RIC regimen given to older pts with AML in CR1 on a prospective multi-center phase II trial conducted by the Alliance (formerly Cancer and Leukemia Group B (CALGB)) and the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The study, activated in 2004, was initially limited to recipients of a matched related donor (MRD) graft but was amended in 2006 to include matched unrelated donor grafts (URD). The primary endpoint of the study was 2-year DFS. We hypothesized that DFS at 2-years would exceed 20% and powered the study to detect a 2-year DFS probability of 35% for URD recipients. We focused the primary analysis on URD recipients since the majority of older pts require an URD graft. Eligible pts were from 60–74 years old inclusive, had AML in CR1 following induction chemotherapy, availability of a 6/6 MRD or 8/8 URD, and absence of significant end-organ damage prior to transplantation. Adverse events (AE) were initially recorded according to NCI-CTCAE v3.0, amended to v4.0 in 10/2010. Accrual was completed in 12/2011. 132 pts were registered at 21 centers and 123 transplanted (MRD (47%); URD (53%). All donor grafts were mobilized and collected following G-CSF (PBSC). The median age of pts was 65 (range 60–74) and 76 pts (62%) were male. At diagnosis, 67% had an intermediate risk karyotype, 20% adverse risk, <1% favorable, and in 11% data were missing. More than 90% achieved CR following standard “7+3” based induction. CR1 was achieved after 1 (59%) or 2 (41%) induction cycles. Consolidation therapy was administered for one (50%) or two (24%) cycles and 17% received no consolidation with data missing in 9%. All but the initial 8 MRD recipients (who received fludarabine and busulfan alone) were conditioned with the same regimen containing fludarabine (30mg/m2/day × 5), busulfan (6.4mg/kg IV total dose), and antithymocyte globulin (ATG; thymoglobulin) (7.5mg/kg total dose). Only one case of primary graft failure was reported. With a median follow-up of 3.3 yrs, the results in the 123 transplanted pts are depicted below: Event Cumulative incidence at 100 days* or 2yrs† 95% CI Acute GVHD 2-4 9.4%* 4.1–15% Acute GVHD 3-4 3.4%* 1.2–6.7% Chronic GVHD 26%† 17–34% Relapse 47%† 37–57% Treatment related mortality (TRM) 14%† 7.2–21% Event Probability at 2 yrs 95% CI DFS 39% 30–50% DFS URD only 38% 26–55% Overall survival (all pts) 46% 36–57% The rates of both acute and chronic GVHD as well as TRM were relatively low. There were 81 grade 3–5 non-hematologic AE recorded, including 7 grade 5 (4 infections, 1 each cardiac, pulmonary, and second malignancy). Relapse was the most common cause of death. In conclusion, the results of this first prospective US cooperative group trial conducted in a homogeneously treated group of older AML patients in CR1 demonstrate the feasibility and effectiveness of RIC allografting using MRD or URD PBSC grafts. DFS appears better following a RIC allograft compared to results achieved historically after conventional therapies, warranting prospective comparison in pts with contemporary cytogenetic and molecular disease characterization. Future research should also focus on preventing disease relapse after RIC allografting in this population. Disclosures: Devine: Sanofi: Honoraria, Research Funding. Off Label Use: Antithymocyte globulin for GVHD prophylaxis is included in the abstract. Vij:Millennium: Speakers Bureau. Shea:Otsuka: Research Funding.

Background: Antibodies constitute an important drug development platform for drugs to treat several ophthalmic, oncologic, and immunologic conditions, but due to limitations inherent in antibody production and structure, a wide range of other protein binding scaffolds are being investigated. Designed ankyrin repeat proteins (DARPins) are simple to produce and offer a range of advantages over antibodies because of their stability, high binding affinity, and rigid structure. Objective: DARPins are being developed for a wide variety of medical applications, and the most studied molecule, abicipar pegol, is used to treat chorioretinal vascular diseases. This mini-review will discuss the current state of DARPin technology and will summarize drug development with a focus on abicipar. Methods: PubMed searches with keywords “DARPin” and “designed ankyrin repeat proteins” were performed and the reference lists of identified articles were examined for additional research material. Studies using DARPin molecules were identified at Clinicaltrials. gov. Non-peer reviewed data were found through Google searches of pertinent websites. Results: Abicipar prevents angiogenesis by binding all isoforms of vascular endothelial growth factor (VEGF)-A with single-digit picomolar affinity. Abicipar has a long intraocular half-life in rabbits and has produced promising results in pre-clinical studies. Pivotal phase III registration trials for the treatment of neovascular age-related macular degeneration are ongoing and a phase II/III trial for the treatment of diabetic macular edema has been announced. Conclusion: Abicipar pegol has the potential to effectively treat chorioretinal vascular conditions with an extended duration of action beyond those of currently used anti-VEGF drugs.