Clinical therapeutics
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Clinical therapeutics · Mar 2019
ReviewPreoperative Frailty Evaluation: A Promising Risk-stratification Tool in Older Adults Undergoing General Surgery.
General surgical procedures are among the most commonly performed operations in the United States. Despite advances in surgical and anesthetic techniques and perioperative care, complications after general surgery in older adults remain a significant cause of increased morbidity, mortality, and health care costs. Frailty, a geriatric syndrome characterized by multisystem physiologic decline and increased vulnerability to stressors and adverse clinical outcomes, has emerged as a plausible predictor of adverse outcomes after surgery in older patients. Thus, the goal of this topical review is to evaluate the evidence on the association between preoperative frailty and clinical outcomes after general surgery and whether frailty evaluation may have a role in surgical risk-stratification in vulnerable older patients. ⋯ Evidence supports the further development of preoperative frailty evaluation as a risk-stratification tool in older adults undergoing general surgery. Research is urgently needed to quantify and differentiate the predictive ability of validated frailty instruments in the context of different general surgical procedures and medical acuity and in conjunction with existing surgical risk indices widely used in clinical practice. Practical applicability of frailty instrument as well as geriatrics-centered outcomes need to be incorporated in future studies in this line of research. Furthermore, clinical care pathways that integrate frailty assessment, geriatric medicine focused perioperative and postoperative management, and patient-centered interdisciplinary care models should be investigated as a comprehensive intervention approach in older adults undergoing general surgery. Finally, early implementation of palliative care should occur at the outset of hospital encounter in frail older patients who present with indications for emergent general surgery.
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Clinical therapeutics · Mar 2019
Multicenter StudyA New Sustained-release, 3-Month Leuprolide Acetate Formulation Achieves and Maintains Castrate Concentrations of Testosterone in Patients With Prostate Cancer.
This clinical trial investigated the effectiveness, pharmacokinetic properties, and safety profile of leuprolide acetate 22.5-mg depot, a new 3-month leuprolide depot formulation, as androgen deprivation therapy for patients with prostate cancer. ⋯ Leuprolide acetate 22.5-mg depot was effective in achieving and maintaining testosterone suppression. Safety and tolerability profiles were consistent with established profiles of androgen deprivation therapy. Clinical Trials.gov identifier: NCT01415960.
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Clinical therapeutics · Mar 2019
Risk Factors of QTc Prolongation in Women With Hormone Receptor‒positive/Human Epidermal Growth Factor Receptor 2‒negative Metastatic Breast Cancer: A Retrospective Analysis of Health Care Claims Data.
In addition to biomarker status, treatment selection for metastatic breast cancer (mBC) includes individual patient and clinical characteristics such as tumor burden, timing of disease recurrence, and comorbidities. Women with mBC may take medications that can increase the risk of drug-induced toxicities, including prolongation of cardiac repolarization (prolongation of QT interval). Corrected QT (QTc) prolongation, a toxicity associated with many cancer treatments, can lead to potentially life-threatening ventricular arrhythmias. As such, it is important to identify patients at risk for QTc prolongation due to comorbid conditions, concomitant medications, or electrolyte abnormalities. This real-world study estimated the proportion of women with hormone receptor‒positive (HR+)/human epidermal growth factor receptor 2‒negative (HER2‒) mBC who may be at risk of developing QTc prolongation. Results in the elderly are also included. ⋯ This analysis of real-world data indicates that almost 1 in 3 women with HR+/HER2‒ mBC had congenital long QT syndrome, cardiovascular disease, and/or electrolyte abnormalities or received a concomitant medication that could increase the risk of developing QTc prolongation. The risk factors for congenital long QT syndrome, cardiovascular disease, or electrolyte abnormalities were more common in older patients. This analysis emphasizes the importance of individualized benefit/risk assessment during treatment decisions, especially when considering drugs with known or possible QTc prolongation risk.
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Clinical therapeutics · Mar 2019
Outpatient Antimicrobial Stewardship: Targets for Community-acquired Pneumonia.
Community-acquired pneumonia (CAP) is one of the leading causes of death in the United States. The primary objective of this study was to determine the prevalence of appropriate diagnosis and treatment of outpatients treated for CAP. Knowledge of problems with CAP treatment can be helpful in developing stewardship initiatives to improve care of outpatients with CAP. ⋯ Improvement in prescribing is needed for CAP. An outpatient stewardship program that targets patients with risk factors for DRSP would improve adherence to guidelines.
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Clinical therapeutics · Feb 2019
ReviewThe Case for Real-world Evidence in the Future of Clinical Research on Chronic Myeloid Leukemia.
In light of recently published guidelines from the US Food and Drug Administration (FDA) on the communication of real-world data (RWD) and real-world evidence (RWE) to support regulatory decision making, it is important to understand how such data are developed, the limitations of these data, and how to best use RWD to improve patient care. Historically, the use of RWE has been approached with skepticism because of its often-retrospective nature compared with data from conventional randomized controlled trials (RCTs). This review discusses the role and function of RWE and RWD in clinical research. We summarize the types of RWE used in clinical research, outline the challenges and limitations involved with these data, and suggest how these types of analyses can supplement results from clinical trials to foster a more complete understanding of a drug or disease area of interest. In particular, we focus on the role of RWE in investigating chronic myeloid leukemia (CML) and tyrosine kinase inhibitor therapy for CML. ⋯ Real-world studies are different from conventional RCTs and therefore provide insight into distinct aspects of treatment and patient outcomes. Together with results from clinical trials, RWE can help to illustrate a more complete picture of the tolerability, effectiveness, and impact of a drug. The recently published guidelines indicate that the FDA expects a growing role for RWE.