Citations

Objective:The prognostic role of electroencephalography during and after targeted temperature management in postcardiac arrest patients, relatively to other predictors, is incompletely known. We assessed performances of electroencephalography during and after targeted temperature management toward good and poor outcomes, along with other recognized predictors.Design:Cohort study (April 2009 to March 2016).Setting:Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester, MN).Patients:Consecutive comatose adults admitted after cardiac arrest, identified through prospective registries.Interventions:All patients were managed with targeted temperature management, receiving prespecified standardized clinical, neurophysiologic (particularly, electroencephalography during and after targeted temperature management), and biochemical evaluations.Measurements and Main Results:We assessed electroencephalography variables (reactivity, continuity, epileptiform features, and prespecified “benign” or “highly malignant” patterns based on the American Clinical Neurophysiology Society nomenclature) and other clinical, neurophysiologic (somatosensory-evoked potential), and biochemical prognosticators. Good outcome (Cerebral Performance Categories 1 and 2) and mortality predictions at 3 months were calculated. Among 357 patients, early electroencephalography reactivity and continuity and flexor or better motor reaction had greater than 70% positive predictive value for good outcome; reactivity (80.4%; 95% CI, 75.9–84.4%) and motor response (80.1%; 95% CI, 75.6–84.1%) had highest accuracy. Early benign electroencephalography heralded good outcome in 86.2% (95% CI, 79.8–91.1%). False positive rates for mortality were less than 5% for epileptiform or nonreactive early electroencephalography, nonreactive late electroencephalography, absent somatosensory-evoked potential, absent pupillary or corneal reflexes, presence of myoclonus, and neuron-specific enolase greater than 75 µg/L; accuracy was highest for early electroencephalography reactivity (86.6%; 95% CI, 82.6–90.0). Early highly malignant electroencephalography had an false positive rate of 1.5% with accuracy of 85.7% (95% CI, 81.7–89.2%).Conclusions:This study provides class III evidence that electroencephalography reactivity predicts both poor and good outcomes, and motor reaction good outcome after cardiac arrest. Electroencephalography reactivity seems to be the best discriminator between good and poor outcomes. Standardized electroencephalography interpretation seems to predict both conditions during and after targeted temperature management.

10 Background: Our objective was to evaluate the cost-utility of 3 lymphadenectomy (LND) strategies in the treatment of low-risk endometrial cancer (EC). Methods: A decision analysis model compared 3 LND strategies in women undergoing minimally invasive surgery (MIS) for EC: 1) routine LND in all pts; 2) selective LND based on intraoperative frozen section, in which 60% of pts undergo LND; and 3) sentinel lymph node mapping (SLN) based on a published algorithm, in which 15% of pts map unilaterally (requiring a contralateral LND) and 5% don’t map (requiring bilateral LND). Costs and outcomes were obtained from published literature and Medicare reimbursement rates. Costs categories consisted of hospital, physician, operating room, pathology, and lymphedema treatment. Effectiveness was defined as 3-year disease-specific survival adjusted for the impact of lymphedema (utility = 0.8) on quality of life. Incremental cost-effectiveness ratios (ICERs) per quality-adjusted life years (QALYs) gained were calculated. QALYs and costs were discounted at an annual 3% rate. Results: For the estimated 40,000 women undergoing surgery for low-risk EC each year in the US, the annual cost of routine LND, selective LND, and SLN is $722 million, $681 million, and $656 million respectively. In the base case scenario, routine LND had a cost of $18,041 and an effectiveness of 2.79 QALYs. Selective LND had a cost of $17,036 and an effectiveness of 2.81 QALYs, while SLN had a cost of $16,401 and an effectiveness of 2.87 QALYs. With a difference of $1,005 and 0.02 QALYs, selective LND was both less costly and more effective than routine LND, dominating it. However, with the lowest cost and highest effectiveness, SLN dominated the other modalities and was the most cost-effective strategy. No ICER could be determined. These findings were robust to multiple one- and two-way sensitivity analyses varying the rates of lymphedema and LND, surgical approach (open or MIS), lymphedema utility, and costs. Conclusions: Compared to routine and selective LND, SLN had the lowest cost and highest quality-adjusted survival, making it the most cost-effective strategy in the management of low-risk EC.

e569 Background: O is a PARP inhibitor that has received breakthrough designation for use in mCRPC based on a study in which a subset of 16 patients with DNA repair defects had an 80% response rate. O is an oral tablet taken twice daily. Studies have demonstrated that compliance with oral agents is often poor, and the less frequent contact with medical staff increases the risk of toxicities when compared to IV therapies. This is compounded by a bias where oral medications are thought of as less toxic than IV medications. The toxicities of O include myelosuppression, nausea, vomiting, and fatigue. Our practice employs a pharmacist to conduct weekly phone calls for toxicity management, monitor patient adherence, and monitor for drug-drug interactions. We report our experience with patient adherence, toxicities, and response with O in mCRPC. Methods: A single institution, retrospective review was performed on 14 mCRPC patients treated with O from November 2015 - October 2016. Adherence and toxicity data were assessed and documented via phone calls conducted by a clinical pharmacist. The primary outcomes were number of missed doses, incidence of toxicities, and dose modifications. The secondary outcome was response rate, defined as a 50% reduction in PSA or radiographic response according to RECIST 1.1 for a duration of greater than 3 months. Results: Patients reported taking 99% of the prescribed doses. The toxicities observed most commonly were fatigue (64%), nausea (57%) and anemia (57%). As a result of toxicities, four patients required a dose reduction to 300 mg BID, three patients required a dose reduction to 200 mg BID and two patients were initiated on 200 mg BID and maintained on that dose until progression. Partial responses were seen in 6 of 14 patients. Conclusions: Our pharmacist led adherence program facilitated timely dose adjustments and high patient adherence. Response rates were comparable to published data.

Purpose To identify approaches to operationalizing the development of competence in Accreditation Council for Graduate Medical Education (ACGME) milestones. Method The authors reviewed all 25 “Milestone Project” documents available on the ACGME Web site on September 11, 2013, using an iterative process to identify approaches to operationalizing the development of competence in the milestones associated with each of 601 subcompetencies. Results Fifteen approaches were identified. Ten focused on attributes and activities of the learner, such as their ability to perform different, increasingly difficult tasks (304/601; 51%), perform a task better and faster (171/601; 45%), or perform a task more consistently (123/601; 20%). Two approaches focused on context, inferring competence from performing a task in increasingly difficult situations (236/601; 29%) or an expanding scope of engagement (169/601; 28%). Two used socially defined indicators of competence such as progression from “learning” to “teaching,” “leading,” or “role modeling” (271/601; 45%). One approach focused on the supervisor’s role, inferring competence from a decreasing need for supervision or assistance (151/601; 25%). Multiple approaches were often combined within a single set of milestones (mean 3.9, SD 1.6). Conclusions Initial ACGME milestones operationalize the development of competence in many ways. These findings offer insights into how physicians understand and assess the developmental progression of competence and an opportunity to consider how different approaches may affect the validity of milestone-based assessments. The results of this analysis can inform the work of educators developing or revising milestones, interpreting milestone data, or creating assessment tools to inform milestone-based performance measures.

Coronary artery aneurysm is defined as a coronary dilation that exceeds the diameter of adjacent segments or the diameter of the patient's largest normal coronary vessel by 1.5×. It is an uncommon disease that has been diagnosed with increasing frequency since the widespread appearance of coronary angiography. The published incidence varies from 1.5% to 5%, suggesting male dominance and a predilection for the right coronary artery. Although several causes have been described, atherosclerosis accounts for ≥50% of coronary aneurysms in adults. Reported complications include thrombosis and distal embolization, rupture, and vasospasm, causing ischemia, heart failure, or arrhythmias. The natural history and prognosis remain unknown, as definitive data are scarce. Controversies persist regarding the use of medical management (antithrombotic therapy) or interventional/surgical procedures. Only some case reports or small case series are available about this condition. The Coronary Artery Aneurysm Registry (CAAR; http://www.ClinicalTrials.gov NCT02563626) is a multicenter international ambispective registry that aims to provide insights on anatomic, epidemiologic, and clinical aspects of this substantially unknown entity. In addition, the registry will assess management strategies (conservative, interventional, or surgical) and their short‐ and long‐term results in a large cohort of patients.Clinical Trial registration: ClinicalTrials.gov. Unique identifier: NCT02563626.

114 Background: We evaluated baseline differences in arm tissue composition (fat mass, lean mass, bone mineral content [BMC] and bone mineral density [BMD]) between the affected and unaffected arms in women with breast cancer-related lymphedema (BRCL). We compared changes in arm tissue composition and self-reported lymphedema symptoms after one-year of weight-lifting vs. usual-care. Methods: We utilized data from the PAL trial that included 141 women with BRCL. Arm tissue composition was quantified using dual-energy x-ray absorptiometry. The severity of lymphedema was quantified using self-report survey. Weight-lifting was performed at community fitness facilities. Results: At baseline, the affected arm had more fat (D= 89.7±21.0g; P < 0.001) and lean mass (D= 149.1±25.3g; P < 0.001), but less BMC (D= -3.2±0.9g; P < 0.001) than the unaffected arm. No difference was observed in BMD. After 12-months of weight-lifting, composition of the affected arm was improved: lean mass (71.2±27.9g; P = 0.01) and BMD (0.01±0.01g; P = 0.02) increased, arm fat percentage decreased (0.01±0.01; P = 0.003). No changes observed in fat mass and BMC. Baseline body mass index and BCRL grade modified the relationship between weight-lifting and tissue composition changes. Increases in lean mass were associated with less severe BCRL symptoms. With every one-percent decrease in arm fat percentage, affected limb volume reduced 13.81mL. Conclusions: Among women with BRCL, affected and unaffected arms differ in tissue composition. These differences may be improved with weight-lifting. Changes in arm tissue composition correlate with improved BCRL symptoms. Investigating the combined effects of exercise and weight-loss on arm tissue composition and BCRL symptoms may provide additional insight to the benefits of lifestyle modification on lymphedema biology. Clinical trial information: NCT00194363.

Aims: The US National Cancer Institute recently developed the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events). PRO-CTCAE is a library of questions for clinical trial participants to self-report symptomatic adverse events (e.g. nausea). The objective of this study is to inform evidence-based selection of a recall period when PRO-CTCAE is included in a trial. We evaluated differences between 1-, 2-, 3-, and 4-week recall periods, using daily reporting as the reference. Methods: English-speaking patients with cancer receiving chemotherapy and/or radiotherapy were enrolled at four US cancer centers and affiliated community clinics. Participants completed 27 PRO-CTCAE items electronically daily for 28 days, and then weekly over 4 weeks, using 1-, 2-, 3-, and 4-week recall periods. For each recall period, mean differences, effect sizes, and intraclass correlation coefficients were calculated to evaluate agreement between the maximum of daily ratings and the corresponding ratings obtained using longer recall periods (e.g. maximum of daily scores over 7 days vs 1-week recall). Analyses were repeated using the average of daily scores within each recall period rather than the maximum of daily scores. Results: A total of 127 subjects completed questionnaires (57% male; median age: 57). The median of the 27 mean differences in scores on the PRO-CTCAE 5-point response scale comparing the maximum daily versus the longer recall period (and corresponding effect size) was −0.20 (−0.20) for 1-week recall, −0.36 (−0.31) for 2-week recall, −0.45 (−0.39) for 3-week recall, and −0.47 (−0.40) for 4-week recall. The median intraclass correlation across 27 items between the maximum of daily ratings and the corresponding longer recall ratings for 1-week recall was 0.70 (range: 0.54–0.82), for 2-week recall was 0.74 (range: 0.58–0.83), for 3-week recall was 0.72 (range: 0.61–0.84), and for 4-week recall was 0.72 (range: 0.64–0.86). Similar results were observed for all analyses using the average of daily scores rather than the maximum of daily scores. Conclusion: A 1-week recall corresponds best to daily reporting. Although intraclass correlations remain stable over time, there are small but progressively larger differences between daily and longer recall periods at 2, 3, and 4 weeks, respectively. The preferred recall period for the PRO-CTCAE is the past 7 days, although investigators may opt for recall periods of 2, 3, or 4 weeks with an understanding that there may be some information loss.