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The treatment landscape for advanced and metastatic melanoma has drastically changed in recent years, with the advent of novel therapeutic options such as immune checkpoint inhibitors and targeted therapies offering remarkable efficacy and significantly improved patient outcomes compared to traditional approaches. Approximately 50% of melanomas harbor activating BRAF mutations, with over 90% resulting in BRAF V600E. Tumors treated with BRAF inhibitor monotherapy have a high rate of developing resistance within six months. Combination therapy with MEK inhibitors helped to mitigate this treatment resistance and led to improved outcomes. Due to the up-regulation of PD-1/PD-L1 receptors in tumors treated with BRAF/MEK inhibitor therapy, further studies included a third combination agent, anti-PD-1/PD-L1 inhibitors. This triple combination therapy may have superior efficacy and a manageable safety profile when compared with single or double agent therapy regimens. Plain Language Summary: Effective treatment of advanced and metastatic melanoma can be challenging. Newer treatment methods for patients with BRAF-mutated tumors include a combination of drugs with different complementary mechanisms. These drugs include BRAF-inhibitors, MEK-inhibitors, and PD-1/PD-L1 inhibitors. When these three medications are used in combination, patients may have better response rates and survival outcomes, when compared to using just one or two of these medications together. Toxicity rates are higher with a triple-medication regimen, so careful patient selection is important to consider. [ABSTRACT FROM AUTHOR]

Background: Opioid misuse is currently plaguing the US. Efforts to reduce this include opioid prescribing education (OPE). Orthopaedic residents often prescribe opioids but, their education is unknown., Methods: A survey was sent to orthoapedic residency program directors (PDs) regarding their program's controlled substance (CS) policies and knowledge of local CS regulations., Results: There were 60 (36.8%) completed surveys. 54 (90.0%) programs allow resident outpatient opioid prescribing. Nine (16.7%) programs require individual DEA registration and 7 (13.0%) were unsure about DEA registrations. State laws regarding PDMP utilization and OPE for fully licensed physicians were correctly answered by 52 (86.7%) and 43 (71.6%), respectively. 27 (45.0%) programs had a mandatory OPE. Six (10.0%) PDs were unsure about a mandatory OPE. 16 (48.5%) programs that did not confirm an OPE were considering adding one., Conclusions: The majority of programs permit residents outpatient opioid prescribing; less than half provide mandatory OPE. Several PDs were unaware local CS prescribing regulations and education. This study demonstrates opportunities to improve OPE among orthopaedic residencies and PDs' knowledge regarding CS regulations., (Copyright © 2019 Elsevier Inc. All rights reserved.)