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Proton pump inhibitors (PPI) are commonly prescribed for many gastrointestinal diseases. A number of case reports have linked PPIs to gynecomastia in men, but large epidemiologic studies are lacking.
To examine the association between central nervous system (CNS)-active medication use and risk of fall-related injury in community-dwelling older adults following dementia onset. Further, to evaluate increased risk at higher doses or with greater number of CNS-active medications classes.
Although few studies have used ketamine for induction and maintenance of pediatric anesthesia, official dosage recommendations are lacking. This study evaluates the outcomes of adult anesthetic doses in a pediatric population through pharmacokinetic modeling and computer simulations in an attempt to recommend an adequate ketamine dosing regimen. Ketamine plasma concentration-time data in 19 children (age 8 months to 16 years; weight 5.5 to 67 kg) were analyzed according to a non-compartmental pharmacokineti...
Over the past decade, use of synthetic cannabinoids (also known as "K2″ and "spice") has grown in popularity nationwide. We describe a multicenter series of six patients admitted with synthetic cannabinoid intoxication displaying similar symptoms and sequelae, all resulting in multiple organ failure. All patients presented with altered mental status and severe rhabdomyolysis, with a peak creatine phosphokinase (CPK) ranging from 4,000 to >320,000 units/L. The majority of patients (5/6) presented with acut...
The optimal pharmacodynamic parameter for prediction of efficacy of vancomycin is the area under the concentration-time curve (AUC), and current published data indicate that dosing based on vancomycin trough concentrations is an inaccurate substitute. In this study, our objective was to compare the achievement of therapeutic target attainment after switching from a trough-based to an AUC-based dosing strategy as a part of our institution's vancomycin-per-pharmacy protocol.
International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Ph
The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram-negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outda...
To assess chronic potentially unsafe medication use among older adults using opioids chronically versus those who did not, to assess the likelihood of chronically using medications to treat adverse effects associated with chronic opioid use, and to characterize the differences in chronic potentially unsafe medication use at three morphine equivalent dose (MED) levels/day (90MED).
Evidence on the cardiotoxicity of nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs)-particularly diclofenac and the newer selective cyclooxygenase (COX)-2 inhibitors-has accumulated over the last decade. Our objective was to examine whether the use of NSAIDs in the Nordic countries changed with the emerging evidence, regulatory statements, and clinical guidelines advocating caution for use of specific NSAIDs.
A recent observational study published in Pharmacotherapy suggests that treatment with an angiotensin receptor blocker (ARB), compared to an angiotensin-converting enzyme (ACE) inhibitor, each combined with statin therapy, substantially reduces cardiovascular events and mortality in patients with newly-diagnosed coronary heart disease. This Alternative Viewpoint describes major biases introduced in the study design that likely contributed to this surprising finding This article is protected by copyright. Al...
Previous studies have identified shifts in gut microbiota associated with atypical antipsychotic (AAP) treatment, which may link AAPs to metabolic burden. Dietary prebiotics such as resistant starch may be beneficial in obesity and glucose regulation, but little is known mechanistically about its ability to modify gut microbiota in AAP-treated individuals. This investigation was undertaken to mechanistically delineate the effects of AAP treatment and resistant starch supplementation on gut microbiota in a p...
Numerous medications interact at serotonin (5-hydroxytryptamine [5-HT]) receptors directly or through off-target interactions, causing mild to severe serotonergic adverse drug events (ADEs), particularly among the elderly. Our objective was to develop a novel molecular-based toxicity scoring system to assess serotonergic burden resulting from concurrently administered drugs. Quantitative methods to assess serotonergic burden may provide a useful clinical tool for improving pharmacotherapy.
Patients with nonvalvular atrial fibrillation (NVAF) often have multiple comorbidities requiring concomitant medications in addition to their oral anticoagulant (OAC). The objective of this study was to evaluate the impact of polypharmacy on the effectiveness and safety of rivaroxaban versus warfarin in patients with NVAF managed in routine clinical practice.
Venous thromboembolism (VTE) occurs frequently in critically ill patients without heparin prophylaxis. Although heparin prevents VTE, VTEs occur frequently despite prophylaxis. Higher heparin dosage may be more effective for preventing VTE.
There are limited markers that could facilitate individualized tacrolimus treatment in the early posttransplantation period. Genetic factors have been found to play critical roles in determining tacrolimus pharmacokinetics.
HLA-B*5701 screening identifies patients at increased risk for abacavir (ABC) hypersensitivity reaction (HSR). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and HIV treatment guidelines in 2008. Company meta-analyses of trials pre-HLA-B*5701 screening reported HSR rates of 4% to 8%. We analyzed the effectiveness of HLA-B*5701 screening on reducing HSR rates using clinical trial, observational (OPERA) cohort, and spontaneous reporting data.
A new postcardiac surgery fluid resuscitation strategy was implemented in our Cardiovascular Intensive Care Unit (CVICU) to implement evidence-based practice. We transitioned from a primarily albumin fluid-based strategy to a lactated Ringer's fluid-based strategy. We sought to determine whether a new postoperative fluid resuscitation strategy significantly altered the fluid composition for postcardiac surgery patients and what effect that would have on fluid resuscitation costs. Secondary outcomes included...
Infections with adenoviruses can result in considerable mortality and morbidity in solid organ transplant recipients. Standard therapy for adenovirus infections in transplant recipients is not established. At our institution, intravenous cidofovir and immunoglobulin have been used to treat disseminated or invasive adenovirus in solid organ and hematopoietic stem cell transplant recipients.
Therapeutic drug management is regularly performed for aminoglycosides in an effort to maximize their effectiveness and safety. The ratio of maximum plasma drug concentration to minimum inhibitory concentration (C /MIC) has long been regarded as the primary pharmacokinetic/pharmacodynamic (PK/PD) index of clinical efficacy for aminoglycosides due to their concentration-dependent killing. In this review, however, we discuss why the area under the plasma concentration-time curve (AUC)/MIC ratio may be a more ...
Central nervous system stimulants are a commonly used, first-line treatment option for attention-deficit/hyperactivity disorder (ADHD). Generally, stimulants are well tolerated, with the most common adverse effects being anorexia and insomnia. However, there are some concerns with long-term use of stimulants, such as potential growth delay. Historically, data regarding this long-term adverse effect have been conflicting. In this article, we reviewed the newer data surrounding the effects of central nervous ...
In 2000, the first biphasic modified-release (MR) formulation of methylphenidate (MPH) was approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). An immediate-release (IR) MPH pulse (22% of the dose) facilitates rapid onset of stimulant action, while the remaining MR portion of the dose provides for day-long duration of efficacy. A wide array of oral MR-MPH products has subsequently been approved that also allows for once daily dosing, though each product is characterized by distinct...
Meropenem-vaborbactam is a new β-lactam/β-lactamase inhibitor combination designed to target Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae. Meropenem-vaborbactam was Food and Drug Administration FDA approved for complicated urinary tract infections (cUTI) in patients 18 years of age or older. An understanding of the pharmacokinetics of meropenem when given in combination with vaborbactam is important to understanding the dosing of meropenem-vaborbactam. Additionally, the safety an...
There are significant clinical and financial consequences to both inadequate and unnecessary exposure to broad-spectrum antibiotics. As such, antimicrobial stewardship programs seek objective, reliable, and cost-effective tests to identify patients at highest or lowest risk for drug-resistant organisms to guide empiric antimicrobial selection. Utilization of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening to rule out MRSA in lower respiratory tract infections has led to significant reduct...
Identify population pharmacokinetics and pharmacodynamic target attainment of gentamicin in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing controlled hypothermia (CH).
Suboptimal Clinical Response Rates with Newer Antibiotics Among Patients with Moderate Renal Impairment: Review of the Literature and Potential Pharmacokinetic and Pharmacodynamic Considerations for Observed Findings.
A number of antibacterial agents have emerged into the United States market in the last two decades to address growing concerns of antimicrobial resistance. These agents have demonstrated noninferiority to comparators for treatment of a range of complicated infections in their respective clinical trials. However, with select agents, a trend of reduced therapeutic efficacy has been observed among study patients with baseline renal impairment. This phenomenon was seen in phase III studies involving ceftazidim...
Omadacycline is a novel aminomethylcycline seeking approval for treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. This article reviews existing data pertaining to the biochemistry, mechanism of action, pharmacokinetics/pharmacodynamics, in vitro activity, and current progress with omadacycline in clinical trials. Omadacycline inhibits protein synthesis by binding to the 30S subunit of the bacterial ribosome at the tetracycline binding site with an a...