Factors That Influence Medical Student Selection of an Emergency Medicine Residency Program: Implications for Training Programs

Objectives:  An understanding of student decision‐making when selecting an emergency medicine (EM) training program is essential for program directors as they enter interview season. To build upon preexisting knowledge, a survey was created to identify and prioritize the factors influencing candidate decision‐making of U.S. medical graduates. Methods:  This was a cross‐sectional, multi‐institutional study that anonymously surveyed U.S. allopathic applicants to EM training programs. It took place in the 3‐week period between the 2011 National Residency Matching Program (NRMP) rank list submission deadline and the announcement of match results. Results:  Of 1,525 invitations to participate, 870 candidates (57%) completed the survey. Overall, 96% of respondents stated that both geographic location and individual program characteristics were important to decision‐making, with approximately equal numbers favoring location when compared to those who favored program characteristics. The most important factors in this regard were preference for a particular geographic location (74.9%, 95% confidence interval [CI] = 72% to 78%) and to be close to spouse, significant other, or family (59.7%, 95% CI = 56% to 63%). Factors pertaining to geographic location tend to be out of the control of the program leadership. The most important program factors include the interview experience (48.9%, 95% CI = 46% to 52%), personal experience with the residents (48.5%, 95% CI = 45% to 52%), and academic reputation (44.9%, 95% CI = 42% to 48%). Unlike location, individual program factors are often either directly or somewhat under the control of the program leadership. Several other factors were ranked as the most important factor a disproportionate number of times, including a rotation in that emergency department (ED), orientation (academic vs. community), and duration of training (3‐year vs. 4‐year programs). For a subset of applicants, these factors had particular importance in overall decision‐making. Conclusions:  The vast majority of applicants to EM residency programs employed a balance of geographic location factors with individual program factors in selecting a residency program. Specific program characteristics represent the greatest opportunity to maximize the success of the immediate interview experience/season, while others provide potential for strategic planning over time. A working knowledge of these results empowers program directors to make informed decisions while providing an appreciation for the limitations in attracting applicants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91198/1/ACEM_1323_sm_DataSupplementS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91198/2/j.1553-2712.2012.01323.x.pd

Allopurinol improves myocardial reperfusion injury in a xanthine oxidase-free model

The ability of allopurinol to protect against reperfusion injury in the heart has usually been attributed to its xanthine oxidase (XO)- inhibiting properties. Human myocardium how- ever has exhibited low levels of XO activity. To investigate the effects of allopurinol in an XO-free model and determine whether pretreat- ment is necessary 12 domestic pigs (15 kg to 20 kg) underwent occlusion of the left circum- flex for 8 minutes followed by reperfusion for 4 hours. One group received allopurinol infusion (5 mg/kg IV) at occlusion over 45 minutes and a control group (n = 6) received a saline infusion (same volume). Left ventricular and aortic pressure electrocardiograms and regional wall motion (sonomicrometry) were monitored throughout the process. Regional blood flow (microspheres) were obtained before during and 5 10 and 30 minutes after ischemia. Occlusion decreased transmural flow at the midpapillary level by 75% (0.28 versus 1.10 mUminute/g). The allopurinol-treated group exhibited a mild generalized hyperemia at 5 minutes (ischemic zone: 1.44 versus 1.10 mU min/g which returned to control levels at 10 and 30 minutes. In contrast the control group was associated with only 80% restoration of resting blood flow at 5 minutes (0.84 versus 1.10 mUmin/g) which stabilized at 63% of control levels at 10 and 30 minutes. When evaluated for the propensity of arrhythmias using an arbitrary arrhythmia score the al- lopurinol group demonstrated no myocardial ectopy when compared with the focal ectopy routinely encountered in the control group at all time intervals. Since pigs have no detectable levels of XO activity allopurinol must exert its protectant effect during myocardial reperfu- sion by an alternative mechanism. Because protection was evident without pretreatment beneficial effects may not necessarily be the result of allopurinol degradation products; therefore pretreatment with allopurinol may not be necessary. These results are clinically important when considering the use of allopuri- nol in an emergent coronary angioplasty or coronary artery bypass grafting. Originally published Journal of the National Medical Association Vol. 87 No. 7 July 199

Activating Inducible T-cell Costimulator Yields Antitumor Activity Alone and in Combination with Anti-PD-1 Checkpoint Blockade

Unlabelled: In recent years, there has been considerable interest in mAb-based induction of costimulatory receptor signaling as an approach to combat cancer. However, promising nonclinical data have yet to translate to a meaningful clinical benefit. Inducible T-cell costimulator (ICOS) is a costimulatory receptor important for immune responses. Using a novel clinical-stage anti-ICOS immunoglobulin G4 mAb (feladilimab), which induces but does not deplete ICOS+ T cells and their rodent analogs, we provide an end-to-end evaluation of the antitumor potential of antibody-mediated ICOS costimulation alone and in combination with programmed cell death protein 1 (PD-1) blockade. We demonstrate, consistently, that ICOS is expressed in a range of cancers, and its induction can stimulate growth of antitumor reactive T cells. Furthermore, feladilimab, alone and with a PD-1 inhibitor, induced antitumor activity in mouse and humanized tumor models. In addition to nonclinical evaluation, we present three patient case studies from a first-time-in-human, phase I, open-label, dose-escalation and dose-expansion clinical trial (INDUCE-1; ClinicalTrials.gov: NCT02723955), evaluating feladilimab alone and in combination with pembrolizumab in patients with advanced solid tumors. Preliminary data showing clinical benefit in patients with cancer treated with feladilimab alone or in combination with pembrolizumab was reported previously; with example cases described here. Additional work is needed to further validate the translation to the clinic, which includes identifying select patient populations that will benefit from this therapeutic approach, and randomized data with survival endpoints to illustrate its potential, similar to that shown with CTLA-4 and PD-1 blocking antibodies. Significance: Stimulation of the T-cell activation marker ICOS with the anti-ICOS agonist mAb feladilimab, alone and in combination with PD-1 inhibition, induces antitumor activity across nonclinical models as well as select patients with advanced solid tumors

Supplementary Table 6 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade

Example TIL marker expression phenotypes from clinical patient case studies of feladilimab monotherapy and in combination with pembrolizumab.</p

Supplementary Figure 2 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade

Flow cytometry gating strategy for ICOS on individual T cell populations.</p

Supplementary Figure 4 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade

Uncropped gel images</p

Supplementary Figure 7 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade

Healthy human donor CD4+ T cells were pre-activated with antiCD3/CD28 for 48 hours and then re-stimulated with plate-bound anti-CD3 in the presence of increasing concentrations of soluble or plate-bound feladilimab or isotype control for 72 hours. IFNg levels were then assessed from cell-free supernatants using Meso Scale Discovery (MSD)-based detection.</p

Supplementary Table 4 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade

Table S4</p

Supplementary Methods from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade

Supplementary Methods</p