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BACKGROUNDRecipients of hematopoietic stem cell transplantation (HSCT) are among the highest consumers of allogeneic red blood cell (RBC) and platelet (PLT) components. The impact of patient blood management (PBM) efforts on HSCT recipients is poorly understood.STUDY DESIGN AND METHODSThis observational study assessed changes in blood product use and patient‐centered outcomes before and after implementing a multidisciplinary PBM program for patients undergoing HSCT at a large academic medical center. The pre‐PBM cohort was treated from January 1 through September 31, 2013; the post‐PBM cohort was treated from January 1 through September 31, 2015.RESULTSWe identified 708 patients; 284 of 352 (80.7%) in the pre‐PBM group and 225 of 356 (63.2%) in the post‐PBM group received allogeneic RBCs (p < 0.001). Median (interquartile range [IQR]) RBC volumes were higher before PBM than after PBM (3 [2‐4] units vs. 2 [1‐4] units; p = 0.004). A total of 259 of 284 pre‐PBM patients (91.2%) and 57 of 225 (25.3%) post‐PBM patients received RBC transfusions when hemoglobin levels were more than 7 g/dL (p < 0.001). The median (IQR) PLT transfusion quantities was 3 (2‐5) units for pre‐PBM patients and 2 (1‐4) units for post‐PBM patients (p < 0.001). For patients with PLT counts of more than 10 × 109/L, a total of 1219 PLT units (73.4%) were transfused before PBM and 691 units (48.8%) were transfused after PBM (p < 0.001). Estimated transfusion expenditures were reduced by $617,152 (18.3%). We noted no differences in clinical outcomes or transfusion‐related adverse events.CONCLUSIONPatient blood management implementation for HSCT recipients was associated with marked reductions in allogeneic RBC and PLT transfusions and decreased transfusion‐related costs with no detrimental impact on clinical outcomes.

The American Board of Anesthesiology (ABA) has been administering an oral examination as part of its initial certification process since 1939. Among the 24 member boards of the American Board of Medical Specialties, 13 other boards also require passing an oral examination for physicians to become certified in their specialties. However, the methods used to develop, administer, and score these examinations have not been published. The purpose of this report is to describe the history and evolution of the anesthesiology Standardized Oral Examination, its current examination development and administration, the psychometric model and scoring, physician examiner training and auditing, and validity evidence. The many-facet Rasch model is the analytic method used to convert examiner ratings into scaled scores for candidates and takes into account how difficult grader examiners are and the difficulty of the examination tasks. Validity evidence of the oral examination includes that it measures aspects of clinical performance not accounted for by written certifying examinations, and that passing the oral examination is associated with a decreased risk of subsequent license actions against the anesthesiologist. Explaining the details of the Standardized Oral Examination provides transparency about this component of initial certification in anesthesiology.

Background:The expression of the receptor tyrosine kinase (RTK) Axl on cancer cells has been associated with poor prognosis and implicated in disease progression. Inhibition of Axl‐RTK with TP‐0903, a high affinity Axl‐RTK inhibitor induces robust apoptosis of several tumors, including chronic lymphocytic leukemia (CLL). Axl‐RTK inhibition has also been found to induce nonspecific immunomodulatory effects in syngeneic tumor models.Aims:We aimed to investigate the impact and downstream effects of Axl‐RTK inhibition on naïve T cells and chimeric antigen receptor T cells (CART), using CD19 directed CART cells (CART19) as a model.Methods:We utilized either PMA/Ionomycin or the CD19+ mantle cell lymphoma cell line, JeKo as a stimulant for naïve T cells and CART19, respectively. Cells were analyzed for cytokine profile, T cell phenotype, and kinetics after the stimulation in the presence or the absence of the Axl‐RTK inhibitor TP‐0903. Regarding in vivo experiment, a relapse JeKo xenograft model was used. Mice were treated with vehicle alone, TP‐0903 alone, CART19 alone, or TP‐0903 + CART19. Three weeks after the treatment, mice were re‐challenged with JeKo as a CART19 relapse model.Results:Stimulation of naïve T cells in the presence of the Axl‐RTK inhibitor TP‐0903 resulted in a significant reduction of Th2 cytokines and downregulation of inhibitory receptors. The differential expansion of either effector T cells or Tregs in the presence of TP‐0903 resulted in a preferential reduction of Tregs (Fig 1A). Axl‐RTK inhibition of CART19 led to Th1 polarization upon stimulation with the JeKo, as evident by the selective reduction of Th2 cytokine. Additionally, this resulted in a reduction of myeloid attracting cytokines, such as CXCL1, IL‐8, IL‐6, and IL‐10, cytokines implicated in the development cytokine release syndrome and neurotoxicity after CART cell therapy and in adaptive resistance to immunotherapy (Fig 1B). TP‐0903 also significantly downregulated inhibitory receptors on activated CARTs (Fig 1C). In our relapsed in vivo model, mice treated with CART19 + TP‐0903 rejected the JeKo challenge while mice received CART19 alone redeveloped disease, suggesting that Axl‐RTK inhibition enhanced CART cell persistence. Peripheral blood analysis of mice after the rechallenge showed a higher number of circulating T cells and lower level of MCP‐1. Western blotting was performed to investigate the downstream effect of Axl‐RTK inhibition on CART19 and it revealed a relatively selective inhibition of LCK on stimulated CART19. Transcriptome analysis of activated CARTs treated with TP‐0903 revealed >100 genes that were differentially expressed compared to untreated cells. Among these, Th cell and Treg polarization genes were significantly altered in activated CARTs treated with TP‐0903.imageFinally, we validated our findings in phase I clinical trial of TP‐0903 (NCT02729298). T cells isolated from 3 cancer patients showed a significant reduction of Tregs and Th1 polarization. This will be further investigated in a planned phase I clinical trial of TP‐0903 in relapsed/refractory CLL (NCT03572634).Summary/Conclusion:We showed for the first time that Axl‐RTK inhibition polarizes T cells into a Th1 functional phenotype, downregulates inhibitory receptors, and reduces myeloid associated cytokine production by CART19. The combination therapy yielded synergistic cytotoxicity against JeKo in vitro and in a CART19 relapse model. These findings encourage further study of Axl‐RTK inhibition with TP‐0903 as an enhancer of T cell immunotherapies.

Abstract Objective Electronic (eHealth) and mobile (mHealth) technologies may be a useful adjunct to clinicians treating patients with chronic pain. The primary aim of this study was to investigate the effects of eHealth and mHealth interventions that do not require clinician contact or feedback on pain-related outcomes recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) guidelines in adults with chronic pain. Methods We searched four databases and included English language randomized controlled trials of ambulatory adults with chronic pain from January, 1 2000, to January 31, 2018, with interventions that are independent of clinician contact or feedback. In the meta-analysis, outcomes were assessed at short- (three months or less), intermediate- (four to six months), and long-term (seven or more months) follow-up. Results Seventeen randomized controlled trials (N = 2,496) were included in the meta-analysis. Both eHealth and mHealth interventions had a significant effect on pain intensity at short- and intermediate-term follow-up. Similarly, a significant but small effect was observed for depression at short- and intermediate-term follow-up and self-efficacy at short-term follow-up. Finally, a significant effect was observed for pain catastrophizing at short-term follow-up. Conclusions eHealth and mHealth interventions had significant effects on multiple short- and intermediate-term outcome measures recommended in the IMMPACT guidelines. Given widespread availability and low cost to patients, clinicians treating patients with chronic pain could consider using eHealth and mHealth interventions as part of a multidisciplinary pain treatment strategy.

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background This repeated cross-sectional survey study was conducted to determine the prevalence of, and factors associated with, burnout, distress, and depression among anesthesiology residents and first-year graduates. We hypothesized that heavy workload and student debt burden were associated with a higher risk of physician burnout, distress, and depression, and that perception of having adequate workplace resources, work–life balance, and social support were associated with a lower risk. Methods Physicians beginning U.S. anesthesiology residency between 2013 and 2016 were invited to take online surveys annually from their clinical anesthesia year 1 to 1 yr after residency graduation. The Maslach Burnout Inventory, the Physician Well-Being Index, and the Harvard Department of Psychiatry/National Depression Screening Day Scale were used to measure burnout, distress, and depression, respectively. Logistic regression analyses were conducted to examine whether self-reported demographics, personal, and professional factors were associated with the risk of burnout, distress, and depression. Results The response rate was 36% (5,295 of 14,529). The prevalence of burnout, distress, and depression was 51% (2,531 of 4,966), 32% (1,575 of 4,941), and 12% (565 of 4,840), respectively. Factors associated with a lower risk of all three outcomes included respondents’ perceived workplace resource availability, (odds ratio = 0.51 [95% CI, 0.45 to 0.57] for burnout; 0.51 [95% CI, 0.45 to 0.56] for distress; 0.52 [95% CI, 0.45 to 0.60] for depression) and perceived ability to maintain work–life balance (0.61 [95% CI, 0.56 to 0.67] for burnout; 0.50 [95% CI, 0.46 to 0.55] for distress; 0.58 [95% CI, 0.51 to 0.65] for depression). A greater number of hours worked per week and a higher amount of student debt were associated with a higher risk of distress and depression, but not burnout. Conclusions Burnout, distress, and depression are notable among anesthesiology residents. Perceived institutional support, work–life balance, strength of social support, workload, and student debt impact physician well-being.

This study compared anesthesiology residency graduates’ written certification examination performance before and after the American Board of Anesthesiology (ABA) introduced the staged examination system. After equating test scores using common test items, the first 2 cohorts (2013, 2014) in the staged system scored 7.1 points and 8.3 points higher than the 2011 baseline cohort in the former examination system. The 2013 and 2014 cohorts’ pass rates (94.2% and 95.9%) were also higher than the 2011 and 2012 cohorts (91.9% and 92.6%) if a common standard had been applied. The staged examination system may be associated with improved knowledge of anesthesiology graduates.

PURPOSEDrug development is becoming increasingly expensive and time consuming. Drug repurposing is one potential solution to accelerate drug discovery. However, limited research exists on the use of electronic health record (EHR) data for drug repurposing, and most published studies have been conducted in a hypothesis-driven manner that requires a predefined hypothesis about drugs and new indications. Whether EHRs can be used to detect drug repurposing signals is not clear. We want to demonstrate the feasibility of mining large, longitudinal EHRs for drug repurposing by detecting candidate noncancer drugs that can potentially be used for the treatment of cancer.PATIENTS AND METHODSBy linking cancer registry data to EHRs, we identified 43,310 patients with cancer treated at Vanderbilt University Medical Center (VUMC) and 98,366 treated at the Mayo Clinic. We assessed the effect of 146 noncancer drugs on cancer survival using VUMC EHR data and sought to replicate significant associations (false discovery rate < .1) using the identical approach with Mayo Clinic EHR data. To evaluate replicated signals further, we reviewed the biomedical literature and clinical trials on cancers for corroborating evidence.RESULTSWe identified 22 drugs from six drug classes (statins, proton pump inhibitors, angiotensin-converting enzyme inhibitors, β-blockers, nonsteroidal anti-inflammatory drugs, and α-1 blockers) associated with improved overall cancer survival (false discovery rate < .1) from VUMC; nine of the 22 drug associations were replicated at the Mayo Clinic. Literature and cancer clinical trial evaluations also showed very strong evidence to support the repurposing signals from EHRs.CONCLUSIONMining of EHRs for drug exposure–mediated survival signals is feasible and identifies potential candidates for antineoplastic repurposing. This study sets up a new model of mining EHRs for drug repurposing signals.

Pain is one of the most commonly experienced and feared symptoms faced by patients with a serious illness. For these patients, intrathecal drug delivery systems (IDDSs) provide greater potency and/or few systemic side effects. However, despite these benefits, the integration and management of IDDS for patients receiving hospice care has not been previous studied. An electronic, 18-question survey was sent to 200 hospice practitioners (physicians, nurse practitioners and nurses) in the state of Minnesota to explore their experience, confidence, and the perceived barriers to caring for patients with IDDS while being cared for on hospice. Providers were identified though mailing lists from the Minnesota Network of Hospice and Palliative Care organization. The survey was administered by the Mayo Clinic Survey Research Center with institutional review board approval. Slightly more than 50% of respondents have ever cared for a patient with an intrathecal pump. If a patient had a pump in place, only 28% of providers expressed confidence in managing their pain. Additionally, only 3 of 10 respondents felt that adjusting an intrathecal pump should be the first option when a patient with an IDDS in place had increased pain. Indeed, the vast majority (over 80%) of respondents preferred the use of systemic therapies for primary pain management. Access to IDDS vendors for changes/refills in the home is identified as another barrier with over 50% of respondents either unaware of an available vendor or reporting no vendor available. There are numerous self-reported barriers to ongoing use of IDDS with patients receiving hospice care.

6575 Background: Delays in diagnosis (dx) and treatment (tx) affect breast cancer (BC) outcomes. We sought to identify factors associated with delays among young women, who do not undergo routine screening and often have pregnancy or breastfeeding-related breast changes that may mask a BC. Methods: The Young Women’s Breast Cancer Study is a multicenter, prospective cohort that enrolled 1302 women with newly dx BC age ≤40 between 2006-2016. Women reported the method and timing of cancer detection on the baseline survey. 231 were ineligible or excluded due to missing information. Among those reporting self-detected cancers, using multivariable regression we evaluated factors associated with delays ≥90 days (d) from symptom to presentation (self delay) and presentation to dx (care delay); in stage 0-III BC we evaluated delays ≥60d from dx to tx (tx delay). Results: 1071 eligible women had median age at dx of 37 yrs (17-40) and 74% reported self-detected cancers. Self delay or care delay ≥90d was reported in 17% and 13%, respectively. Factors inversely associated with self delay included pregnancy at dx (vs nulliparous, OR 0.10, CI 0.01-0.78) and perceived financial comfort (vs not, OR 0.62, CI 0.41-0.93). Women dx ≤1 year post-partum who breastfed (vs nulliparous, OR 2.60, CI 1.14-5.93) and those with a family history of breast/ovarian cancer (vs none, OR 1.79, CI 1.00-3.19) were more likely to have a care delay. Age was inversely associated with care delays (OR 0.94, CI 0.89-0.99). Tx delay was reported by 10% (105/1015), and associated with being single (vs partnered, OR 1.61, CI 1.02-2.56 ), non-white (vs white, OR 1.85, CI 1.09-3.13) and having Stage 0 BC (vs stage 1, OR: 3.08, CI 1.65-5.77); women with stage 3 BC (vs stage 1, OR 0.13, CI 0.03-0.56) were less likely to have a tx delay. Conclusions: In this cohort, most young women with BC underwent timely dx and tx initiation. Women dx ≤1 year post-partum who breastfed were more likely to experience a care delay, likely because lactational changes may mask BC signs and symptoms. The associations of perceived financial status with self delay and non-white race with tx delay underscore the need for additional support to ensure timely care for underserved populations with the goal of eliminating disparities in outcomes.