Pharmacotherapy
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Review
Midostaurin: A New Oral Agent Targeting FMS-Like Tyrosine Kinase 3-Mutant Acute Myeloid Leukemia.
Acute myeloid leukemia (AML), a clonal hematologic malignancy that results in bone marrow failure, is the most common acute leukemia in adults (median age of diagnosis 67 yrs), and treatment options, especially in the elderly population, are limited. Induction chemotherapy with 7 + 3, the combination of continuous-infusion cytarabine and intermittent dosing of an anthracycline administered over 7 and 3 days, respectively, has remained the standard of care since its introduction in 1973 in the United States. Midostaurin is a first-generation FMS-like tyrosine kinase 3 (FLT3) inhibitor (TKI) that was approved by the U. ⋯ In addition to being evaluated in combination with conventional chemotherapy, midostaurin has been studied as monotherapy, in combination with the hypomethylating agents azacitidine and decitabine, and as single-agent maintenance. Studies evaluating midostaurin in the maintenance setting after allogeneic stem cell transplantation are underway. Midostaurin is the first oral multitargeted TKI to improve overall survival in patients with FLT3-mutant AML and represents an important addition to the limited armamentarium against AML.
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Comparative Study
A Comparison of Insulin Doses for the Treatment of Hyperkalemia in Patients with Renal Insufficiency.
To compare the safety and efficacy of 5 units versus 10 units of insulin for the treatment of hyperkalemia in patients with renal insufficiency. ⋯ In patients with renal insufficiency and hyperkalemia, 5 units of insulin reduced serum potassium to the same extent as 10 units of insulin but with a lower rate of hypoglycemia. Further controlled studies are needed to confirm these findings.
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Ketamine may be used to manage pain and agitation that is refractory to what are usually considered traditional agents such as fentanyl, propofol, benzodiazepines, and dexmedetomidine; however, literature describing the use of ketamine continuous infusions for this purpose in critically ill trauma patients is limited. ⋯ Although the use of ketamine in critically ill mechanically ventilated adult trauma patients was associated with decreased opioid use, it was also associated with increased use of dexmedetomidine and ziprasidone to achieve and maintain sedation. Further examination of clinical outcomes associated with these differences in drug use in a larger population of trauma patients is warranted before routine use of ketamine for analgesia and sedation can be recommended.
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Ipilimumab, pembrolizumab, and nivolumab are checkpoint inhibitors (CPIs) that activate T-cell-mediated immune response. CPI can provide durable benefits to some cancer patients with melanoma, renal cell cancer, non-small cell lung cancer, or a growing list of other cancers. However, CPI treatment is also associated with adverse immune-mediated reactions (IMRs) that can be life-threatening. This pharmacovigilance analysis aims to characterize IMR signals in relation to CPI treatment. ⋯ Cancer immunotherapy with CPIs is associated with a multitude of IMRs, especially colitis and pneumonitis. Individual CPIs had variable IMR signals, and pharmacoepidemiologic studies are required to evaluate the identified signals.
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Pediatric opioid and benzodiazepine withdrawal are avoidable complications of pain and sedation management that is well described in the literature. To prevent withdrawal from occurring, practitioners regularly use a steady decrease of pain and sedation medications, also known as a weaning or tapering schedule. The weaning schedule is highly variable based on clinician preference and is usually dependent on the clinician. ⋯ The use of a standardized opioid-weaning protocol reduced withdrawal rates compared with nonstandardized weaning plans. Benzodiazepine weaning was inconsistently evaluated and may have affected study outcomes. Identified areas of improvement include the use of newer withdrawal assessment tools validated in the older pediatric population and standardized withdrawal assessment and reporting.