Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is an inclusive term describing diverse syndromes of multiple etiologies with the common features of thrombocytopenia and microangiopathic hemolytic anemia. Other organ involvement, including renal failure, neurologic abnormalities, and gastrointestinal symptoms, is common. Adverse reactions to drugs increasingly are reported as a potential cause of TTP-HUS. More than 50 drugs and other substances have been associated with the development of TTP-HUS, but many case reports are difficult to interpret because there is uncertainty regarding the diagnosis of TTP-HUS and because there is uncertainty regarding the relation of drug exposure to the onset of TTP-HUS. A systematic analysis of reports of drug-associated TTP-HUS will be required to better understand the strength of clinical evidence linking drugs to the etiology of TTP-HUS. In this review, five drugs that have been the subject of the most and the most recent reports of drug-associated TTP-HUS are discussed: mitomycin C, cyclosporine, quinine, ticlopidine, and clopidogrel. The clinical features of TTP-HUS associated with these drugs are different, suggesting two principal mechanisms by which drugs may cause TTP-HUS: dose-related toxicity (mitomycin C, cyclosporine), and immune-mediated reaction (quinine, ticlopidine, clopidogrel). The role of plasma exchange is uncertain, but this treatment is appropriate because of the high mortality and morbidity of drug-associated TTP-HUS. Recognition of a drug-associated etiology in a patient with TTP-HUS is critical to avoid re-exposure and recurrent illness.
Although clinical knowledge on the effectiveness of bevacizumab is limited, early data indicate that it is a promising agent, with a novel mechanism of action, for patients with metastatic cancer, including colorectal cancer.
Immune checkpoint inhibitors are designed to restore a patient's own antitumor immune response that has been suppressed during tumor development. The first monoclonal antibodies against the immune checkpoint programmed death 1 (PD‐1) receptor, nivolumab and pembrolizumab, are now approved for clinical use. Both agents are indicated for the treatment of advanced melanoma, as well as for the treatment of metastatic non–small cell lung cancer (NSCLC). Nivolumab is also approved for the treatment of advanced renal cell carcinoma. In patients with melanoma, these agents result in objective response rates of ~25–40%, with durable responses lasting more than 2 years in some cases. Results from phase III trials have shown improved survival with nivolumab versus standard‐of‐care chemotherapy in both patients with advanced melanoma and those with advanced NSCLC. In patients with advanced melanoma, both PD‐1 inhibitors (nivolumab and pembrolizumab) have shown improved survival versus ipilimumab. PD‐1 inhibitors are associated with adverse events that have immune etiologies, with grade greater than 3 adverse events typically reported in 16% or less of patients. However, most immune‐mediated adverse events (including grade 3–4 adverse events) can be managed by using published management algorithms without permanent discontinuation of the agent. As nivolumab and pembrolizumab enter the clinic, and with more PD‐1 pathway agents in development for a range of tumor types, this review aims to provide pharmacists with a basic understanding of the role of PD‐1 in modulating the immune system and their use in the cancer treatment. The most recent clinical efficacy and safety data are discussed, highlighting the response characteristics distinctive to immune checkpoint inhibitors, along with pharmacokinetic and pharmacodynamic data and cost considerations.
Objectives. To implement an audience response system in a dual-campus classroom that aggregated data during graded (attendance and quizzes) and non-graded classroom activities (formative quizzes, case discussions, examination reviews, and team activities) and explore its strengths, weaknesses, and impact on active learning. Design. After extensive research, an appropriate audience response system was selected and implemented in a dual-classroom setting for a third-year required PharmD course. Students were assigned a clicker and training and policies regarding clicker use were reviewed. Activities involving clicker use were carefully planned to simultaneously engage students in both classrooms in real time. Focus groups were conducted with students to gather outcomes data. Assessment. Students and faculty members felt that the immediate feedback the automated response system (ARS) provided was most beneficial during non-graded activities. Student anxiety increased with use of ARS during graded activities due to fears regarding technology failure, user error, and academic integrity. Summary. ARS is a viable tool for increasing active learning in a doctor of pharmacy (PharmD) program, especially when used for non-graded class activities. Faculty members should proceed cautiously with using ARS for graded classroom activities and develop detailed and documented policies for ARS use.
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