No abstract

e21674 Background: Carfilzomib (Carf)is a novel proteasome inhibitor (PI) that is approved for patients with relapsed multiple myeloma (RMM) who have failed ≥ 1 prior lines of therapy. The incidence and seriousness of Carf associated cardiotoxicity (CT) is not well defined. We hypothesize that CT is more frequent than that seen with other PIs. We performed systematic review of Carf literature with meta-analysis to determine its incidence and overall risk. Methods: Initial search of literature led to a total of 175 Carf related articles. However, we used 29 publicatons; phase I/II, phase II and phase III (n = 3) clinical trials in which Carf was used as monotherapy or in combination with other chemo agents. We excluded phase I studies and studies without CT data. Incidence rates and odds ratios (OR) were calculated with either fixed effect or random effect model based on the heterogeneity of included studies. Toxicity was reported according to CTCAE v4.0. Results: A total of 4560 patients with various hematological and solid malignancies were included. Incidence of all grades and high grades (≥ 3) CT (including arrhythmias, CHF with LVEF drop, and coronary syndrome) were 7.8% and 4.72%, respectively. When compared to control group taken from phase III clinical trials, the risk of developing CT due to Carf was significantly higher with OR of 1.90 and 2.03 (P < 0.01) for all grades and high grades, respectively. Moreover, incidence of CT was significantly higher in Carf combination therapy (9.85%) compared to Carf monotherapy (5.40%) (P = 0.01). Furthermore, incidence of high grade CT was 7.5% and 5% with and without concomitant immunomodulatory agent (IMiD), respectively (P = 0.004). There was no variation in the incidence of CT among newly diagnosed versus RMM (P = 0.6), and no Carf dose effect. Mortality rate associated with cardiotoxicity was 1.5%. Conclusions: Overall incidence of Carf related CT seems to be higher than that reported with other PIs. Although, the pathophysiology is poorly understood, this trend could potentially be secondary to irreversible nature of proteasome inhibition by Carf. There seems to be a significant increase in CT with combination of Carf and an IMiD. Prior therapies and higher Carf doses have no effect on CT incidence.

Purpose: Traditionally, the morbidity and mortality conference (M&MC) is a forum where possible medical errors are discussed. Although M&MCs can facilitate identification of opportunities for systemwide improvements, few studies have described their use for this purpose, particularly in residency training programs. This paper describes the use of M&MC case review as a quality improvement activity that teaches system-based practice and can engage residents in improving systems of care. Methods: Internal medicine residents at a tertiary care academic medical center reviewed 347 consecutive mortalities from March 2014 to September 2017. The residents used case review worksheets to categorize and track causes of mortality, and then debriefed with a faculty member. Selected cases were then presented at a larger interdepartmental meeting and action items were implemented. Descriptive statistics and thematic analysis were used to analyze the results. Results: The residents identified a possible diagnostic mismatch at some point from admission to death in 54.5% of cases (n= 189) and a possible need for improved management in 48.0% of cases. Three possible management failure themes were identified, including failure to plan, failure to communicate, and failure to rescue, which accounted for 21.9%, 10.7 %, and 10.1% of cases, respectively. Following these reviews, quality improvement initiatives proposed by residents led to system-based changes. Conclusion: A resident-driven mortality review curriculum can lead to improvements in systems of care. This novel type of curriculum can be used to teach system-based practice. The recruitment of teaching faculty with expertise in quality improvement and mortality case analyses is essential for such a project.

Ceftriaxone is a commonly used antibiotic in hospitals for the treatment of pneumonia, urinary tract infection, bacteremia, meningitis, skin, and soft tissue infection. It can be associated with common allergic reactions like skin rash, itching, and, rarely, angioedema. Ceftriaxone-induced immune hemolytic anemia (IHA) is a rare and potentially fatal complication if not identified and managed in time. We report a case of ceftriaxone-induced IHA in a young woman.