Carfilzomib is a second-generation proteasome inhibitor (PI) that is approved for patients with relapsed or refractory multiple myeloma (RRMM) who failed ≥1 prior lines of therapy. We performed a systematic review of carfilzomib literature with meta-analysis to determine cumulative incidence of cardiotoxicity. After the literature search, we included a total of 29 eligible phase I/II, phase II and phase III clinical trials which used carfilzomib. The cumulative incidence and overall odds ratios (OR) were calculated with random effect model, using ‘R’ software with metaphor package. A total of 4164 patients with various malignancies were included. The overall estimated cumulative incidence of cardiotoxicity was 8.68% and 4.92%, respectively, for all-grade and high-grade (≥ grade 3) toxicity, which seems higher than other PIs. Compared to control group, the odds of developing cardiotoxicity due to carfilzomib was significantly higher with OR of 2.03 (95% CI: 1.19–3.46, p = .010) and 2.04 (95% CI: 1.31–3.17, p = .002) for all-grades and high grades, respectively. Concomitant immunomodulatory agents seem to increase the risk of cardiotoxicity (high-grade cardiotoxicity 6.45% and 4.34% with and without concomitant immunomodulatory agents, respectively (p = .033)). There was no variation in the incidence of cardiotoxicity among newly diagnosed versus RRMM (p = .38), and high versus standard dose carfilzomib (p = .86).

Background: The recommendations of the American Board of Internal Medicine Foundation’s “Choosing Wisely^®” initiative recognize the importance of improving the appropriateness of testing behavior and reducing the number of duplicate laboratory tests. Objective: To assess the effectiveness of an electronic medical record Best Practice Alert (BPA or “pop up”) intervention aimed at reducing duplicate laboratory tests and hospital costs. Design: Comparison of the number of duplicated laboratory tests performed on inpatients before and after the intervention. Setting: University of Florida Health Shands Hospital, Gainesville, FL, USA, during 2014–2017. Intervention: The electronic medical record intervention was a BPA pop-up alert that informed the ordering physician if a recent identical order already existed along with the “ordering time”, “collecting time”, “resulting time”, and the result itself. Main outcome measures: Percentage change in the number of inpatient duplicate orders of selected clinical biochemistry tests and cost savings from reduction of the duplicates. Student’s t-test and beta-binomial models were used to analyze the data. Results: Results from the beta-binomial model indicated that the intervention reduced the overall duplicates by 18% (OR=0.82, standard error=0.016, P-value<0.000). Percent reductions in 9 of the 17 tests were statistically significant: serum hemoglobin A1C level, vitamin B12, serum erythrocyte sedimentation rate, serum folate, serum iron, lipid panel, respiratory viral panel, serum thyroid stimulating hormone level, and Vitamin D. Additionally, important cost savings were realized from the reduction of duplicates for each lab test (with the exception of CRP) with an estimated overall savings of $72,543 over 17 months in the post-intervention period. Conclusions: The present study included all hospital inpatients and covered 17 clinical laboratory tests. This rather simple and low-cost intervention resulted in significant reductions in percentage duplicates of several tests and resulted in cost savings. The study also highlights the role of hospitalists in quality improvement.

Background: The incidence of hepatocellular carcinoma (HCC) is increasing. Development of newer therapeutic modalities has changed the paradigm of HCC treatment in recent years. So, the aim of our study is to analyze the impact of these treatment modalities into the survival of HCC patients, based on the stage of HCC in real life practice. Methods: We analyzed the data from the SEER database: Incidence − SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973–2013 varying). Relative survival rates (RSRs) and hazard ratios (HRs) were measured for patients diagnosed with HCC between 2001 and 2013. Rates were compared between pre sorafenib [2001–2007] and post sorafenib [2008–2013] eras. Results: A total of 50,088 patients (21,435 in pre sorafenib era and 28,653 in the post-sorafenib era) were included with HCC from SEER database. The median relative survival for the entire population was 14 months with 5-year RSR of 21.20%; 11 months for those diagnosed in 2001–2007 with 5-year RSR 19.30% and 17 months for those diagnosed in 2008–2013 with 5-year RSR 22.40% (P<0.01). This survival improvement was largely limited to HCC patients with single nodule (5-year RSR; 35.1% vs. 37.00% for pre and post sorafenib era respectively; P value <0.01) and multiple nodules without vascular invasion (5-year RSR; 19.90% vs. 22.60% for pre and post sorafenib era respectively; P value <0.01). RSR remained extremely poor with no significant improvement for advanced stage HCC who had vascular invasion (P=0.37) or distant metastasis (P=0.10), respectively for pre and post sorafenib era in each category. Survival improved since 2008, for HCC patients who received either no surgical intervention (P<0.01) or received tumor-directed therapy (P<0.01), however, it remained significantly poor compared to the patients who received lobectomy or hepatectomy and transplant. Approximately 70% of patients from our study population did not receive any HCC directed surgical intervention and among this, more than 40% of patients were with single nodule in the liver. Conclusions: Survival in patients with HCC has improved since 2008, which is limited to early stage HCC. Survival of advanced stage HCC patients is extremely poor and has not shown any significant improvement since the approval of sorafenib, emphasizing the need for better therapeutic options. Not receiving any surgical intervention is associated with significantly poor prognosis. Large numbers of early stage HCC patients were not able to receive surgical interventions. This can impose a significant financial burden, as these patients would progress on to the advanced stage, where treatment options are very limited and not as cost-effective. This emphasizes the need for further research to identify various barriers and the possible need for healthcare policy changes.

Efficacy and safety of carfilzomib in relapsed and/or refractory multiple myeloma: systematic review and meta-analysis of 14 trials Efficacy and safety of carfilzomib in relapsed and/or refractory multiple myeloma: systematic review and meta-analysis of 14 trials

A 62-year-old woman with a history of orthotopic liver transplantation for cirrhosis secondary to auto-immune hepatitis 3 months prior, presented with fever and new-onset seizures. Her maintenance immunosuppressive therapy included mycophenolate mofetil 500 mg twice a day, tacrolimus 1 mg