Pharmacotherapy
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Review
A Novel Use of Olaparib for the Treatment of Metastatic Castration-Recurrent Prostate Cancer.
Although mortality from prostate cancer has declined over the past 20 years as a result of early detection and treatment, the 5-year survival rate for men with prostate cancer who develop metastatic disease is only 29%. Current treatment options for metastatic castration-recurrent prostate cancer (mCRPC) are associated with toxicity and a limited durable response; therefore, additional lines of efficacious and minimally toxic therapy are needed. Olaparib, a poly(adenosine 5'-diphosphate) ribose polymerase (PARP) inhibitor, received a U. ⋯ In this review, we describe current therapies for mCRPC, the rationale for anti-PARP therapies, the pharmacology of olaparib for prostate cancer, clinical trials of olaparib for mCRPC, our clinical experience with olaparib for prostate cancer at a comprehensive cancer center, and future directions of olaparib for the treatment of mCRPC. Olaparib may constitute a promising treatment to prolong survival in patients with mCRPC, with an acceptable adverse effect profile. As the role of PARP inhibition in prostate cancer and other malignancies becomes further elucidated, olaparib may be shown to be beneficial for other patient populations.
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Comparative Study
Intravenous-only or Intravenous Transitioned to Oral Antimicrobials for Enterobacteriaceae-Associated Bacteremic Urinary Tract Infection.
To characterize antibiotic regimens utilized for bacteremic Enterobacteriaceae urinary tract infections and assess treatment failure associated with intravenous-only compared to intravenous transitioned to oral antibiotic treatment. ⋯ Intravenous transitioned to oral treatment (intravenous/oral) was associated with a shorter length of stay and fewer hospital antibiotic days compared with intravenous-only therapy. Transitioning from intravenous to oral antibiotic therapy is a viable treatment option to consider for patients with bacteremic Enterobacteriaceae urinary tract infection.
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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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To determine whether early administration of adjuvant β-lactam in combination with vancomycin (COMBO) affects clinical outcomes compared to standard vancomycin therapy alone (STAN) among patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection. ⋯ Receipt of COMBO therapy did not decrease the rate of clinical failure but was associated with expedited bacteremia clearance. Early adjuvant β-lactam therapy deserves continued evaluation and clinical consideration.
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As delirium is a common manifestation in critically ill patients and is associated with worse clinical outcomes, we sought to characterize the reversibility of delirium after discontinuation of sedation and to determine whether sedation-associated delirium that rapidly reverses impacts clinical outcomes. ⋯ Despite the cessation of medications for continuous sedation, delirium persisted for the majority of patients and was associated with worse outcomes, which attests to the importance of strategies to minimize sedation.